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Biomedical subjects

M Duke

Publications and source records attributed to M Duke.

At least 19 recordsLinked to original sources
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↗
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↗
PubMed1993

A revised HindIII map and sequence analysis of a large 'left-hand' non-essential region of the rabbit poxvirus genome.

Sequence analysis of a 21.5 kb region of the left-hand non-essential region of rabbit poxvirus (RPV) was performed to analyze the structure and gene organization of this region. Initial mapping and cloning studies revealed that the early published HindIII maps are incorrect in that the location of the terminal HindIII B and C fragments, as previously published, are reversed. The sequence of this region was compared to similar regions of several strains of vaccinia virus. The results indicate that this region of RPV has a high degree of homology with a similar region of vaccinia. Analysis of the translated open reading frames (ORFs) has facilitated the detection of several previously unreported ORFs related to human complement proteins. In addition, two defective copies of a homologue of the 77 kDa cowpox virus (CPV) host range gene which allows CPV to grow on Chinese hamster ovary cells have been detected, suggesting a gene duplication has occurred. However, one copy of this gene is segmented into three separate ORFs. Analysis has also identified a large number of indirect repeat elements. A possible role of these repeats in the generation of deletions and gene duplications is suggested.

Amino Acid Sequence↗
PubMed1992

Production of biologically active recombinant human lactoferrin in Aspergillus oryzae.

We report the production of recombinant human lactoferrin in Aspergillus oryzae. Expression of human lactoferrin (hLF), a 78 kD glycoprotein, was achieved by placing the cDNA under the control of the A. oryzae alpha-amylase promoter and the 3' flanking region of the A. niger glucoamylase gene. Using this system, hLF is expressed and secreted into the growth medium at levels up to 25 mg/l. The recombinant lactoferrin is indistinguishable from human milk lactoferrin with respect to its size, immunoreactivity, and iron-binding capacity. The recombinant protein appears to be appropriately N-linked glycosylated and correctly processed at the N-terminus by the A. oryzae secretory apparatus. Lactoferrin is the largest heterologous protein and the first mammalian glycoprotein expressed in the Aspergillus system to date. Hence, this expression system appears suitable for the large-scale production and secretion of biologically active mammalian glycoproteins.

Amino Acid Sequence↗
PubMed1990

A unique mental health network for Victorian aboriginal people.

The Victorian Aboriginal Mental Health Network (VAMHN) is a unique mental health programme for Aboriginal people in Australia. The network was set up in 1987. The services and programmes developed include a community consultation service, a psychiatric inpatient unit; and educational, evaluative and research programmes. Utilisation of the network has steadily increased and the demand for both primary and secondary consultations continues to grow.

Adult↗
PubMed1990

Chemosensitivity testing of fresh human leukemia cells using both a dye exclusion assay and a tetrazolium dye (MTT) assay.

Chemosensitivity testing using a DEA was performed on 91 leukemia samples from 70 patients with leukemia. In 55 patients, comparison of in-vitro results with actual response of the patient was made. There was good correlation in 82% of the cases, the results being highly significant p less than 0.001. The MTT assay was also adapted for the chemosensitivity testing and the usefulness of this assay was evaluated by comparing the results to the DEA for 24 of the samples. Survival results produced by the two assays were very similar. The MTT procedure was also found to be equally effective as the DEA as a predictive assay of chemosensitivity.

Antineoplastic Agents↗
PubMed1988

Chronic mexiletine therapy for suppression of ventricular arrhythmias.

One hundred patients with a 70% or greater reduction of ventricular premature contractions (VPCs) from baseline during 12 weeks of mexiletine therapy were continued on treatment for an additional 9 months. Fifteen patients did not have follow-up examinations. The response of the remaining 85 patients during this extended period of open-label mexiletine administration is described. Holter recordings were scheduled at 3-month intervals during this period. At these examinations, between 69 and 80% of patients maintained the same 70% or greater level of VPC suppression observed at the start of the 9-month treatment period. Mean and median levels of VPCs/h at each examination were significantly reduced from premexiletine levels throughout the study (p less than 0.0001). Blood tests and electrocardiographic intervals did not vary. The most frequently used dosage of mexiletine during each 3-month treatment period was 600 mg/day (50.0-55.6% of patients). Side effects warranted discontinuation of therapy in 8% (8/97) of patients, while in 25% (22/85), clinical evaluation resulted in a change in dosage level. Within a setting similar to that of clinical practice, long-term mexiletine administration for non-life-threatening ventricular arrhythmias was effective and well tolerated.

Cardiac Complexes, Premature↗