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Biomedical subjects

M Duke

Publications and source records attributed to M Duke.

At least 19 recordsLinked to original sources
PubMed2006

Investigation of recombinant Schistosoma japonicum paramyosin fragments for immunogenicity and vaccine efficacy in mice.

Schistosoma japonicum paramyosin, a 97 kDa myofibrillar protein, is a recognized vaccine candidate against schistosomiasis. To improve its expression and to identify protective epitopic regions on paramyosin, the published Chinese Schistosoma japonicum paramyosin cDNA sequence was redesigned using Pichia codon usage and divided into four overlapping fragments (fragments 1, 2, 3, 4) of 747, 651, 669 and 678 bp, respectively. These gene fragments were synthesized and expressed in Pichia pastoris (fragments 2 and 3) or E. coli (fragments 1 and 4). The recombinant proteins were produced at high level and purified using a two-step process involving Ni-NTA affinity chromatography and gel filtration. BALB/c mice were immunized subcutaneously three times at 2-week-intervals with the purified proteins formulated in adjuvant Quil A. The protein fragments were highly immunogenic, inducing high, though variable, ELISA antibody titres, and each was shown to resemble native paramyosin in terms of its recognition by the anti-fragment antibodies in Western blotting. The immunized mice were subjected to cercarial challenge 2 weeks after the final injection and promising protective efficacy in terms of significant reductions in worm burdens, worm-pair numbers and liver eggs in the vaccinated mice resulted. There was no apparent correlation between the antibody titres generated and protective efficacy, as all fragments produced effective but similar levels of protection.

Animals↗
PubMed2003

Linkage disequilibrium mapping provides further evidence of a gene for reading disability on chromosome 6p21.3-22.

Linkage disequilibrium (LD) mapping was used to follow up reports of linkage between reading disability (RD) and an 18 cM region of chromosome 6p21.3-22. Using a two-stage approach, we tested for association between RD and 22 microsatellite markers in two independent samples of 101 (Stage 1) and 77 (Stage 2) parent/proband trios in which RD was rigorously defined. The most significant replicated associations were observed between combinations of markers D6S109/422/1665 (Stage 1, P=0.002 (adjusted for multiple testing); Stage 2, P=0.0001) and D6S506/1029/1660 (Stage 1, P=0.02 (adjusted), Stage 2, P=0.0001). The only two-marker association observed in both samples was with D6S422/1665 (P=0.01, 0.04). No single marker showed replicated association but D6S506 produced values of P=0.01 and 0.08 which were significant when combined (P=0.02). We observed weaker and less consistent evidence of association in a region of confirmed linkage to RD in previous studies. The most consistently significant haplotypic association D6S109/422/1665, showed association with single-word reading, spelling, phonological awareness, phonological decoding, orthographic accuracy and random automised naming, but not with vocabulary or Attention Deficit Hyperactivity Disorder. Our findings strongly support the presence of a gene contributing to RD in a region of chromosome 6 between markers D6S109 and D6S1260, but do not rule out the presence of a gene between D6S1556 and MOG.

Adolescent↗
PubMed2001

Familial Tetralogy of Fallot caused by mutation in the jagged1 gene.

Tetralogy of Fallot (ToF) is the most common form of complex congenital heart disease, occurring in approximately 1 in 3000 live births. Evaluation of candidate loci in a large kindred segregating autosomal dominant ToF with reduced penetrance culminated in identification of a missense mutation (G274D) in JAG1, the gene encoding jagged1, a Notch ligand expressed in the developing right heart. Nine of eleven mutation carriers manifested cardiac disease, including classic ToF, ventricular septal defect with aortic dextroposition and isolated peripheral pulmonic stenosis (PPS). All forms of ToF were represented, including variants with pulmonic stenosis, pulmonic atresia and absent pulmonary valve. No individual within this family met diagnostic criteria for any previously described clinical syndrome, including Alagille syndrome (AGS), caused by haploinsufficiency for jagged1. All mutation carriers had characteristic but variable facial features, including long, narrow and upslanting palpebral fissures, prominent nasal bridge, square dental arch and broad, prominent chin. This appearance was distinct from that of unaffected family members and typical AGS patients. The glycine corresponding to position 274 is highly conserved in other epidermal growth factor-like domains of jagged1 and in those of other proteins. Its substitution in other proteins has been associated with mild or atypical variants of disease. These data support either a relative loss-of-function or a gain-of-function pathogenetic mechanism in this family and suggest that JAG1 mutations may contribute significantly to common variants of right heart obstructive disease.

Amino Acid Sequence↗
PubMed2001

On the fast track.

It has been suggested in nursing literature that a bachelor's degree should be the pre-requisite to professional nursing education and registration. The perceived advantages of graduates entering the nursing profession led faculty in the School of Nursing La Trobe University to introduce in 1997 an innovative two-year Bachelor of Nursing (BN) program, believed to be the first in Australia, for graduates of other disciplines. A problem-based learning (PBL) approach was selected to facilitate the teaching learning process. Data to evaluate the progress of the accelerated students were collected by examining their previous degree background, conducting a focus group discussion mid year and comparing the students' academic results with those completing the traditional three-year course. Findings indicate that students in the accelerated course were highly motivated but experienced significant stress. In part the stress emanated from the need to identify their own learning needs. However, despite their concerns most accelerated students scored at least as well both clinically and academically as traditional students. Moreover, in six of the seven final year subjects each group studied the accelerated students performed better.

Australia↗
PubMed2001

Students' perceptions of learning outcomes from group-based, problem-based teaching and learning activities.

OBJECTIVE: A study aimed at exploring the variation in perceptions of learning outcomes reported by undergraduate nursing students enrolled in a problem-based learning subject in a pre-registration Bachelor of Nursing course (BN). METHOD: Students were asked to respond to four open-ended questions which focussed on their learning outcomes in the different teaching/learning modalities of the subject. Data were analysed in two phases using a modified phenomenographic analysis. In the first phase a set of categories of description were developed from the student responses to questions related to the learning modalities. In the second phase the individual responses were classified in terms of the categories. Finally, correlations between the learning modalities were identified. In this paper the approach to analysis, the process of category identification and the correlations between the learning modalities will be described and the implications for further research and teaching will be discussed. RESULTS: The findings indicated that there were two distinct groups of student responses. Inward focussed students who described outcomes in terms of their own learning and students whose focus was outward i.e. describing learning in terms of patient care and how learning relates to that care. Another important result shows the relationship between the learning modalities and outcomes. From the students' perspective, the most sophisticated outcomes of the lectures and laboratories were ideas and skills to be used and applied in clinical settings. Whereas, the group-based activities in which clinical problems were presented to the students in the form of Situation Improvement Packages (SIPS) focussed their attention on the clinical setting which constituted a preparation for the realities of clinical practice. CONCLUSION: The findings from this study indicate that students perceive their learning in the group based teaching/learning modality (SIPS) as effective in focussing them on the reality of their role in the clinical practice environment while lectures and laboratories provided the skills and knowledge required for this setting.

Curriculum↗
PubMed2001

The questioning skills of clinical teachers and preceptors: a comparative study.

AIM OF THE STUDY: The purpose of this study, conducted as partial requirement for a Master of Nursing Studies Degree, was to explore, describe and compare the level of questions asked by clinical teachers and preceptors. BACKGROUND: Questioning is one of many teaching/learning strategies thought to facilitate the development of critical thinking skills which are integral to nursing practice. As such the type and number of questions asked have implications for student learning. Currently in Melbourne, Australia, many undergraduate nursing degree courses utilize both clinical teachers and preceptors to facilitate student learning in the clinical setting. DESIGN: A comparative descriptive design was used. Participants were given three acute care patient scenarios involving an undergraduate nursing student, as part of a questionnaire, and asked to identify the questions they would ask the student in relation to the scenario. FINDINGS: Data revealed that the clinical teachers had considerably more years of experience in their role and higher academic qualifications than did the preceptors. The clinical teachers also asked a greater number of questions overall and more from the higher cognitive level. Despite this, the findings suggest that both clinical teachers and especially preceptors need to increase the number of higher level questions they ask. CONCLUSIONS: Based on the findings of this study, it is evident that there is a need for further comparative studies into the questioning skills of clinical teachers and preceptors. Also, these two groups require education about the importance of higher level questioning for student learning as well as how to ask questions generally.

Education, Nursing, Baccalaureate↗
PubMed2000

Pentobarbital-induced modulation of flexor and H-reflexes in spinal rats.

Electrophysiological recordings of the H-reflex and nonnociceptive flexion reflex were obtained from pentobarbital-anesthetized Intact rats and from both, anesthetized and unanesthetized groups of Acute and Chronic Spinal rats. Results showed that the flexor, but not H-reflex, of Chronic Spinal rats was significantly larger than that of all other groups, which did not differ among themselves. The antispastic drug baclofen dose-dependently decreased the flexion response of Chronic Spinal rats (A(50)=4.3 mg/kg+/-2.1 and 9.0 mg/kg).

Adjuvants, Anesthesia↗
PubMed2000

Family-based association mapping provides evidence for a gene for reading disability on chromosome 15q.

Family-based association mapping was used to follow up reports of linkage between reading disability (RD) and a genomic region on chromosome 15q. Using a two-stage approach, we ascertained 101 (stage 1) and 77 (stage 2) parent-proband trios, in which RD was characterized rigorously. In stage 1, a set of eight microsatellite markers spanning the region of putative linkage was used and a highly significant association was detected between RD and a three-marker haplotype (D15S994/D15S214/D15S146: P and empirical P < 0.001). A significant association with the same three-marker haplotype was also observed in the second-stage sample (P = 0.009, empirical P = 0.006). Our data therefore provide strong evidence for one or more genes contributing to RD being located in the vicinity of the region including D15S146 and D15S994. In addition, our results provide support for association analysis being a useful method to map susceptibility loci for complex disorders.

Chromosome Mapping↗
PubMed2000

James Jackson an American physician in London, 1799-1800.

James Jackson (1777-1867) was a prominent physician in Massachusetts during the first half of the nineteenth century. Early in his career, he had traveled to London to complete his medical studies. A search of libraries and archives on both sides of the Alantic has uncovered hitherto unpublished and little known information about his experiences on his journey and while abroad (1799-1800). Presentation of this material not only serves to supplement what is already known about Jackson but in addition heightens our understanding and awareness of contemporary medical issues of his day.

History, 18th Century↗
PubMed1999

Dissociation of (-) baclofen-induced effects on the tail withdrawal and hindlimb flexor reflexes of chronic spinal rats.

We previously reported that the antinociceptive effect of the GABA(B) receptor agonist, (-)baclofen, in chronic spinal rats depended on the route of administration. That is, subcutaneous (SC) injections significantly increased the latency of the thermally elicited tail withdrawal (tail flick, TF) reflex, whereas spinal (intrathecal, IT) injections did not. The present studies attempted to determine the reason for this differential response. The possible contribution of a peripheral component to the systemic effect was evaluated, but was not supported by negative results of intradermal (-)baclofen injections (50 and 500 microg) into the tail skin of chronic spinal rats. A spinal site of action was indicated when pretreatment with 30 microg, IT of the GABA(B) receptor antagonist, phaclofen, significantly reduced the antinociceptive effect of SC (-)baclofen in both chronic spinal (5 mg/kg) and intact rats (2 mg/kg). Moreover, direct IT injections of (-)baclofen in chronic spinal rats produced a modest, but statistically significant increase in TF latency at doses of 0.06, 0.12, 0.3, and 0.6 microg, but not 1.2 microg. In the same spinal preparation, the flexor response was significantly reduced by IT injection of 0.6 and 1.2 microg, but not lower doses of 0.3 and 0.12 microg. These results provide the first quantitative, electrophysiological evidence of an antispastic effect of IT (-)baclofen in an in vivo, unanesthetized animal model. Second, the data show a separation between an antinociceptive effect of low spinal doses and an antispastic/muscle relaxant effect at higher doses, which may account for the results of our prior report. Finally, the data are also consistent with behavioral reports of antiallodynic/analgesic effects of low-dose baclofen, and may be relevant to the electrophysiological evidence of a preferential presynaptic action of low-dose (-)baclofen at the primary afferent synapse.

Analgesics↗
PubMed1999

Comparison of morphine-induced effects on thermal nociception, mechanoreception, and hind limb flexion in chronic spinal rats.

The effect of systemic morphine on 3 behaviors in the same group of chronic spinal rats was examined: the tail-flick (TF) reflex to a noxious thermal stimulus, limb withdrawal (LW) to mechanoreceptor (von Frey hair) stimulation, and hind limb flexion (flexor reflex [FR]) elicited by innocuous electrical stimulation of the toes. Compared with intact rats, the potency of morphine on both the TF and the hind paw (but not the forepaw) LW response was significantly reduced. Morphine's effect on the FR depended on the dose. The lowest dose (1.0 mg/kg) produced no change, 4.0 mg/kg decreased response magnitude by approximately 50% (indicating an antispastic effect), and 8.0 mg/kg increased flexor magnitude by 100%. The concurrent TF and FR assays revealed a dissociation of morphine's effects in that the highest dose (8.0 mg/kg) significantly inhibited the nociceptive TF response but facilitated the FR in the same chronic spinal rats. This outcome may be relevant to the phenomenon of "opioid-related myoclonus" recently described in cancer patients, which "was highly associated with nerve dysfunction due to spinal cord lesions" (S. Mercadante, 1998, p. 6).

Animals↗
PubMed1999

A preliminary investigation of the construct of psychopathic personality (psychopathy) in chimpanzees (Pan troglodytes).

Although the construct of psychopathy has received considerable attention in humans, its relevance to other animals is largely unknown. We developed a measure of psychopathy for use in chimpanzees (Pan troglodytes), the Chimpanzee Psychopathy Measure (CPM), and asked 6 raters to complete this index on 34 chimpanzees. The CPM (a) demonstrated satisfactory interrater reliability and internal consistency; (b) exhibited marginally significant sex differences (males > females); (c) correlated positively with measures of extraversion, agreeableness, and observational ratings of agonism, sexual activity, daring behaviors, teasing, silent bluff displays, and temper tantrums, and negatively with observational ratings of generosity; and (d) demonstrated incremental validity above and beyond a measure of dominance. Although further validation of the CPM is needed, these findings suggest that the psychopathy construct may be relevant to chimpanzees.

Age Factors↗
PubMed1998

Recurrent abdominal pain: a potential precursor of irritable bowel syndrome in adolescents and young adults.

OBJECTIVES: To assess symptoms of irritable bowel syndrome (IBS) in patients with recurrent abdominal pain (RAP) 5 years after their initial evaluation, to identify the relation of IBS symptoms to functional disability and health service use, and to determine the extent to which IBS symptoms are associated with life stress and poor psychosocial adjustment. METHODS: Patients with RAP (n = 76) and control subjects (n = 49) completed a telephone interview; measures included the Bowel Disease Questionnaire, the Functional Disability Inventory, the Life Events Questionnaire, the Family Inventory of Life Events, the Center for Epidemiological Studies Depression Scale, the Self-Perception Profile for Adolescents, and the Health Resources Inventory. RESULTS: Five years after the initial evaluation, patients with RAP reported significantly more episodes of abdominal pain than did control subjects, as well as significantly higher levels of functional disability, school absence, and clinic visits for abdominal distress. Female patients with RAP were more likely than female control subjects to meet the Manning criteria for IBS. Among patients with RAP, higher levels of IBS symptoms were associated with significantly greater functional disability, more clinic visits, more life stress, higher levels of depression, and lower academic and social competence. CONCLUSION: Female patients with a history of RAP may be at increased risk of IBS during adolescence and young adulthood. Among adolescents and young adults with a history of RAP, IBS symptoms are likely to be associated with high levels of disability and health service use.

Abdominal Pain↗
PubMed1997

Two amyloid precursor protein transgenic mouse models with Alzheimer disease-like pathology.

Mutations in the amyloid precursor protein (APP) gene cause early-onset familial Alzheimer disease (AD) by affecting the formation of the amyloid beta (A beta) peptide, the major constituent of AD plaques. We expressed human APP751 containing these mutations in the brains of transgenic mice. Two transgenic mouse lines develop pathological features reminiscent of AD. The degree of pathology depends on expression levels and specific mutations. A 2-fold overexpression of human APP with the Swedish double mutation at positions 670/671 combined with the V717I mutation causes A beta deposition in neocortex and hippocampus of 18-month-old transgenic mice. The deposits are mostly of the diffuse type; however, some congophilic plaques can be detected. In mice with 7-fold overexpression of human APP harboring the Swedish mutation alone, typical plaques appear at 6 months, which increase with age and are Congo Red-positive at first detection. These congophilic plaques are accompanied by neuritic changes and dystrophic cholinergic fibers. Furthermore, inflammatory processes indicated by a massive glial reaction are apparent. Most notably, plaques are immunoreactive for hyperphosphorylated tau, reminiscent of early tau pathology. The immunoreactivity is exclusively found in congophilic senile plaques of both lines. In the higher expressing line, elevated tau phosphorylation can be demonstrated biochemically in 6-month-old animals and increases with age. These mice resemble major features of AD pathology and suggest a central role of A beta in the pathogenesis of the disease.

Alzheimer Disease↗
PubMed1996

A biological and immunological comparison of Chinese and Philippine Schistosoma japonicum.

A comparison was made of the host (BALB/c mice)-parasite relationship of a Chinese mainland (Anhui) strain and Philippine (Sorsogon) strain of Schistosoma japonicum. Differences in fecundity, infectivity, prepatency, host survival and susceptibility to praziquantel were examined. The mean percentage of worms establishing was 40.0 and 34.4% for Chinese and Philippine S. japonicum, respectively. Egg laying commenced on days 26 and 28 after infection with the Chinese or Philippine strain, respectively. Significant differences in the total number of eggs and number of eggs per worm pair laid were observed. In terms of the number of eggs per worm pair and host survival, the Chinese strain was more virulent than the Philippine in BALB/c mice. Praziquantel treatment reduced worm burdens by 80-90% in both strains. No significant differences were observed in murine antibody responses against the 2 strains. Irradiated Chinese cercarial vaccines were protective only against homologous challenge; irradiated Philippine cercarial vaccines were not protective, confirming earlier findings that this strain is neither able to induce nor able to act as a target of irradiated cercariae-mediated vaccination. Antibody responses and immunoblot profiles in vaccinated mice were similar, regardless of the strain of parasite used.

Animals↗
PubMed1996

Clinical evaluation--difficulties experienced by sessional clinical teachers of nursing: a qualitative study.

Evaluation of nursing students in the clinical field requires the clinical teacher to make judgements regarding student progress in a number of areas. In this study concepts of role theory, oppressed group behaviour and the ethics of caring emerged and were used as conceptual frameworks to interpret the data relating to the evaluation of undergraduate students. The number of experienced faculty available for clinical teaching and evaluation has become inadequate and a large number of casual or sessional clinical teachers are employed to teach students in the clinical field. Despite the well documented problems associated with clinical teaching and the use of inexperienced clinical teachers, sessional clinical teachers are nevertheless expected to evaluate student success in meeting the clinical requirements of the nursing course, often resulting in disparate decisions for students. A phenomenological study was carried out using unstructured interviews and written clinical scenarios, to explore the evaluation process from the perspective of the sessional clinical teachers. Research findings indicate that although the sessional clinical teachers were skilled at identifying student problems, they were reluctant to make difficult evaluation decisions, due to low self-esteem, role conflict and their ethic of caring. It seems that gender socialization, patriarchal dominance and apprenticeship training had effected their confidence in their own decision making. The implications of such findings are of concern for the ongoing credibility and integrity of nursing courses, as clinical teachers have an influence on the nursing profession through the preparation of its practitioners.

Clinical Competence↗
PubMed1995

Intracellular accumulation of beta-amyloid in cells expressing the Swedish mutant amyloid precursor protein.

beta-Amyloid (beta A) is a normal metabolic product of the amyloid precursor protein (APP) that accumulates in senile plaques in Alzheimer's disease. Cells that express the Swedish mutant APP (Sw-APP) associated with early onset Alzheimer's disease overproduce beta A. In this report, we show that expression of Sw-APP gives rise to cell-associated beta A, which is not detected in cells that express wild-type APP. Cell-associated beta A is rapidly generated, is trypsin-resistant, and is not derived from beta A uptake, indicating that it is generated from intracellular processing of Sw-APP. Intracellular and secreted beta A are produced with different kinetics. The generation of intracellular beta A is partially resistant to monensin and a 20 degrees C temperature block but is completely inhibited by brefeldin A, suggesting that it occurs in the Golgi complex. Monensin, brefeldin A, and a 20 degrees C temperature block almost completely inhibit beta A secretion without causing increased cellular retention of beta A, suggesting that secreted beta A is generated in a post-Golgi compartment. These results suggest that the metabolism of Sw-APP gives rise to intracellular and secreted forms of beta A through distinct processing pathways. Pathological conditions may therefore alter both the level and sites of accumulation of beta A. It remains to be determined whether the intracellular form of beta A plays a role in the formation of amyloid plaques.

Alzheimer Disease↗