Biomedical subjects
S Whyte
Publications and source records attributed to S Whyte.
Novel Leu723Pro amyloid precursor protein mutation increases amyloid beta42(43) peptide levels and induces apoptosis.
A novel missense mutation, Leu723Pro, in the amyloid precursor protein (APP) gene was discovered in an early-onset Alzheimer's disease family. Expression of L723P mutant APP complementary DNA in CHO cells resulted in a 1.4- to 1.9-fold increased production of the 42(43)-amino acid length amyloid beta peptide compared with the wild-type sequence and was capable of causing apoptosis. The mutation is predicted to alter the luminal transmembrane length and helical arrangement of the APP molecule and thus affect the gamma-secretase cleavage site.
Specialisation in nursing. A survey of reactions of Victorian nurses to the national review of specialist nurse education.
This article reports on the opinions of specialist nurses practising in Victoria toward recommendations proposed in the National Review of Specialist Nurse Education (Specialist Review) (Russell et al 1997). Seventy-five nurses undertaking a range of specialist nursing courses offered by three educational providers (a university, major teaching hospital and professional organisation) completed a survey questionnaire to establish the extent to which they agreed with the major recommendations from the Specialist Review. Results showed strong endorsement for most recommendations but with less agreement about issues of minimum credentials and future provisions. Comparison of responses across age, experience, employment and professional education subgroups identified significant differences of opinions on some recommendations. Findings from this study are discussed in relation to the Specialist Review and to implications for the future development of specialist nursing education in Australia.
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.
Premedication before intubation in UK neonatal units.
AIMS: To establish the extent and type of premedication used before intubation in neonatal units in the United Kingdom. METHODS: A structured telephone survey was conducted of 241 eligible units. Units were subdivided into those that routinely intubated and ventilated babies (routine group) and those that transferred intubated and ventilated babies (transfer group). RESULTS: Of the units contacted, 239 (99%) participated. Only 88/239 (37%) gave any sedation before intubating on the unit and only 34/239 (14%) had a written policy covering this. Morphine was used most commonly (66%), with other opioids and benzodiazepines used less frequently. Of the 88 units using sedation, 19 (22%) also used paralysis. Suxamethonium was given by 10/19 (53%) but only half of these combined it with atropine. Drug doses varied by factors of up to 200, even for commonly used drugs. CONCLUSION: Most UK neonatal units do not sedate babies before intubating, despite evidence of physiological and practical benefits. Only a minority have written guidelines, which prohibits auditing of practice.
The specialist nurse: a classification system.
This paper focuses on the important developments of specialty nursing practice within Australia and reports the results of a recent survey of specialist nurses in Victoria. Debate among the worldwide nursing community reflects confusion and ambiguity about specialist practice. Similarly, variation, duplication and inconsistency characterise the status of specialist nurse education in Australia. This situation contributes to role problems for specialist nurses and may arise from their lack of contribution to the decision making process. Seventy-five nurses undertaking a range of specialist nursing courses offered by three educational providers (a university, major teaching hospital and professional organisation) completed a survey questionnaire to establish the extent to which they agreed with the major recommendations proposed in the National Review of Specialist Nurse Education (Specialist Review) (Russell et al 1997). Despite contention within the profession, specialist nurses in Victoria show support for a unified approach toward definition, title and credentials. The discussion specifically addresses the implications for the future classification of specialist nurses in Australia.
The 3' end CCA of mature tRNA is an antideterminant for eukaryotic 3'-tRNase.
Cytoplasmic tRNAs undergo posttranscriptional 5' and 3' end processing in the eukaryotic nucleus, and CCA (which forms the mature 3' end of all tRNAs) must be added by tRNA nucleotidyl transferase before tRNA can be aminoacylated and utilized in translation. Eukaryotic 3'-tRNase can endonucleolytically remove a 3' end trailer by cleaving on the 3' side of the discriminator base (the unpaired nucleotide 3' of the last base pair of the acceptor stem). This reaction proceeds despite a wide range in length and sequence of the 3' end trailer, except that mature tRNA containing the 3' terminal CCA is not a substrate for mouse 3'-tRNase (Nashimoto, 1997, Nucleic Acids Res 25:1148-1154). Herein, we extend this result with Drosophila and pig 3'-tRNase, using Drosophila melanogaster tRNAHis as substrate. Mature tRNA is thus prevented from recycling through 3' end processing. We also tested a series of tRNAs ending at the discriminator base (-), with one C added (+C), two Cs added (+CC), and CCA added (+CCA) as 3'-tRNase inhibitors. Inhibition was competitive with both Drosophila and pig 3'-tRNase. The product of the 3'-tRNase reaction (-) is a good 3'-tRNase inhibitor, with a KI approximately two times KM for the normal 3'-tRNase substrate. KI increases with each nucleotide added beyond the discriminator base, until when tRNA+CCA is used as inhibitor, KI is approximately forty times the substrate KM. The 3'-tRNase can thus remain free to process precursors with 3' end trailers because it is barely inhibited by tRNA+CCA, ensuring that tRNA can progress to aminoacylation. The active site of 3'-tRNase may have evolved to make an especially poor fit with tRNA+CCA.
Patient-controlled analgesia: epidural fentanyl and i.v. morphine compared after caesarean section.
We have compared patient-controlled epidural fentanyl (PCEF) and patient-controlled i.v. morphine (PCIM) after Caesarean section in 84 patients, in a randomized, double-blind study. All patients had an epidural and an i.v. patient-controlled analgesia (PCA) device, one of which delivered normal saline. Group PCEF received epidural fentanyl 20 micrograms with a 10-min lockout. Group PCIM received i.v. morphine 1 mg with a 5-min lockout. PCA use was lower for PCEF patients (P = 0.0007). The highest pain score recorded at rest for PCEF patients was median 20 (interquartile range 10-33) mm compared with 32 (14-52) mm for PCIM patients (P = 0.02). The highest pain score recorded on coughing was 31 (21-41) mm with PCEF compared with 56 (30-71) mm for PCIM (P = 0.001). There was less nausea (P = 0.02) and drowsiness (P = 0.0003) with PCEF. There was no difference in the overall incidence and severity of pruritus (P = 0.77). However, pruritus started earlier with PCEF.
The effects of age and mood on saccadic function in older individuals.
To investigate the effect of age and mood on saccadic function, we recorded prosaccades, predictive saccades, and antisaccades from 238 cognitively normal, physically healthy volunteers aged 44 to 85 years old. Mood levels were measured using the State-Trait Anxiety Inventory and Center for Epidemiological Studies Depression Scale inventories. Small, but significant, positive relationships with age were observed for the mean latency and associated variability of latency for all types of saccades, as well as the antisaccade error rate. Saccade velocity or accuracy was unaffected by age. Increasing levels of depression had a minor negative influence on the antisaccade latency, whereas increasing levels of anxiety raised the antisaccade error rate marginally.
No association of presenilin-1 intronic polymorphism and Alzheimer's disease in Australia.
We screened 703 Australian subjects for an intronic polymorphism in the presenilin-1 (PS-1) gene. PS-1 intronic allele 1 homozygosity was not associated with individuals with early- or late-onset sporadic Alzheimer's disease (EOAD or LOAD). Carriers for the PS-1 intronic allele 1 were also not associated with significantly increased risk for AD regardless of gender. Our results for the Australian population are consistent with those of recent reports for other populations and do not support the conclusion that the PS-1 intronic polymorphism is associated with AD.
Relative increase in Alzheimer's disease of soluble forms of cerebral Abeta amyloid protein precursor containing the Kunitz protease inhibitory domain.
Although a number of studies have examined amyloid precursor protein (APP) mRNA levels in Alzheimer's disease (AD), no clear consensus has emerged as to whether the levels of transcripts for isoforms containing a Kunitz protease inhibitory (KPI)-encoded region are increased or decreased in AD. Here we compare AD and control brain for the relative amounts of APP protein containing KPI to APP protein lacking this domain. APP protein was purified from the soluble subcellular fraction and Triton X-100 membrane pellet extract of one hemisphere of AD (n = 10), normal (n = 7), and neurological control (n = 5) brains. The amount of KPI-containing APP in the purified protein samples was determined using two independent assay methods. The first assay exploited the inhibitory action of KPI-containing APP on trypsin. The second assay employed reflectance analysis of Western blots. The proportion of KPI-containing forms of APP in the soluble subcellular fraction of AD brains is significantly elevated (p < 0.01) compared with controls. Species containing a KPI domain comprise 32-41 and 76-77% of purified soluble APP from control and AD brains, respectively. For purified membrane-associated APP, 72-77 and 65-82% of control and AD samples, respectively, contain a KPI domain. Since KPI-containing species of APP may be more amyloidogenic (Ho, L., Fukuchi, K., and Yonkin, S. G. (1996) J. Biol. Chem. 271, 30929-30934), our findings support an imbalance of isoforms as one possible mechanism for amyloid deposition in sporadic AD.
Secretion of Alzheimer's disease Abeta amyloid peptide by activated human platelets.
Alzheimer's disease (AD) is characterized by the deposition of Abeta (betaA4) peptides of 39 to 43 amino acid residues, which are normal cellular metabolic products derived by proteolysis of the amyloid precursor protein (APP). The physiologic function of Abeta/APP in vivo is poorly understood. We analyzed human platelets for Abeta production by immunoprecipitation coupled to immunoblotting. A 4-kd Abeta fragment that comigrates with an Abeta40 synthetic peptide and reacts with several antibodies specific for the N- and C-termini of Abeta is detected. The majority of platelet Abeta appears to end at residue 40, as determined by immunoreactivity with an Abeta40-specific antibody. Furthermore, Abeta is secreted upon platelet stimulation with the physiologic agonists thrombin and collagen, together with secretion of soluble APP (sAPP). A comparison between serum and plasma shows a 1.6-fold increase in Abeta levels and a 2.4-fold increase in sAPP levels in serum. This is consistent with the view that platelets are the primary source of circulating Abeta and APP. The release of platelet Abeta by physiologic stimuli suggests that it may play a role in platelet aggregation and coagulation or in the repair mechanisms associated with injury.
Collection and normal levels of the amyloid precursor protein in plasma.
The amyloid precursor protein is contained in platelet alpha granules and released with degranulation. Methods are described to control for amyloid precursor protein release from platelets during blood collection and processing. In normal subjects (n = 97; age range, 44-84 years), the average plasma level of amyloid precursor protein was 6.5 +/- 1.8 ng/ml.
RNase P and 3'-tRNase processing matrices in the analysis of Drosophila transfer RNA D/T loop tertiary contacts.
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An abnormality of plasma amyloid protein precursor in Alzheimer's disease.
beta A4 amyloid deposition in the brain, which is characteristic of Alzheimer's disease (AD), may result from either overexpression of the amyloid protein precursor (APP) or failure of APP to be correctly processed. A blood marker reflecting this abnormal metabolism would be of diagnostic value and would provide a means of monitoring the efficacy of therapeutic interventions. We analyzed immunoblots of plasma APP enriched by heparin-Sepharose chromatography from patients with moderate to severe AD dementia (n = 34) and control subjects (n = 77) and found an approximately 50% increase in the proportion of 130-kd APP species in patients with AD (p less than 0.001), no difference in the 110-kd form, a 15 to 30% decrease in the 65-kd form (p less than 0.001), and a 20 to 35% decrease in the proportion of 42-kd APP (p less than 0.001). These species of APP were soluble, lacked the carboxyl terminus, and the 110- and 42-kd species were shown to be consistent with degradation products derived from the 130-kd species. A comparison of levels of 130-kd plasma APP from moderately to severely demented patients with AD and control subjects distinguished the two groups with a specificity of 87.0% and a sensitivity of 79.4%.
A rare heteromorphism of chromosome 20 and reproductive loss.
A rare centromeric heterochromatic variant of chromosome 20 was encountered during investigations in a couple with repeated miscarriages. The enlarged segment was G and C band positive and stained positively by Giemsa II. In situ hybridisation of the biotinylated alphoid probe D20Z1 specific for the centromere of chromosome 20 to metaphase cells confirmed the presence of amplified sequences adjacent to the centromere. The variant was found to be familial and was evaluated as having no clinical significance.
A review of 20 cases of spastic dysphonia.
Twenty patients with the distinct nosological entity of adductor spastic dysphonia (SD) were seen at St Vincent's Hospital, Sydney over a 6-year period. Nine of these patients also experienced a tremulous voice associated with evidence of an essential tremor (ET) elsewhere, including head, trunk and limbs. The mean age of onset in patients with SD was 45 years and in those with SD with ET was 52 years. In 10 patients the onset was gradual, with the remaining 10 experiencing an abrupt onset, in 3 related to an upper respiratory tract infection and in 7 to psychosocial stress. Factors which frequently resulted in a worsening of speech included stress, public speaking, tiredness, strong emotions, upper respiratory tract infections and prolonged use of the voice. In patients with SD alone temporary relieving factors included spontaneous statements, use of a quiet voice, slow speech, high and low pitch, yawning, chewing, swallowing, laughing and on first waking in the morning. The response to therapy was variable. Two patients underwent recurrent laryngeal nerve sectioning.
[Illness and suffering. Anthropology--a new dimension in nursing. Interview by Grethe Kjaergaard].
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