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M S Clark

Publications and source records attributed to M S Clark.

At least 37 records · Page 2Linked to original sources
PubMed1999

Sequence scanning chicken cosmids: a methodology for genome screening.

The chicken genome is relatively poorly studied at the molecular level. The karyotype 2n=78 is divided into three main chromosomal sub-groups: the macrochromosomes (six pairs), the intermediate microchromosomes (four pairs) and the microchromosomes (29 pairs). Whilst the microchromosome group comprise only 25% of the DNA, increasing evidence is proving that this is disproportionate to their gene content. This paper demonstrates the utility of cosmid sequence scanning as a potential method for analysing the chicken genome, providing an economical method for the production of a molecular map. The GC content, gene density and repeat distribution are analysed relative to chromosomal origin. Results indicate that gene density is higher on the microchromosomes. During the scanning process an example of conserved linkage between chicken and human (12q34.2) has been demonstrated.

Animals↗
PubMed1999

Comparative genomics: the key to understanding the Human Genome Project.

The sequencing of the human genome is well underway. Technology has advanced, such that the total genomic sequence is possible, along with an extensive catalogue of genes via comprehensive cDNA libraries. With the recent completion of the Saccharomyces cerevisiae sequencing project and the imminent completion of that of Caenorhabditis elegans, the most frequently asked question is how much can sequence data alone tell us? The answer is that that a DNA sequence taken in isolation from a single organism reveals very little. The vast majority of DNA in most organisms is noncoding. Protein coding sequences or genes cannot function as isolated units without interaction with noncoding DNA and neighboring genes. This genomic environment is specific to each organism. In order to understand this we need to look at similar genes in different organisms, to determine how function and position has changed over the course of evolution. By understanding evolutionary processes we can gain a greater insight into what makes a gene and the wider processes of genetics and inheritance. Comparative genomics (with model organisms), once the poor relation of the human genome project, is starting to provide the key to unlock the DNA code.

Animals↗
PubMed1999

Changes in family functioning for stroke rehabilitation patients and their families.

This study charted changes over time in the family functioning of a group of stroke rehabilitation patients and their families. Participants were 60 12-month stroke survivors who had undergone an inpatient rehabilitation programme, 46 spouses, and 25 other family members. Participants were assessed at the time of admission to and discharge from rehabilitation, and 6 and 12 months after discharge. The study was undertaken in the rehabilitation unit at Repatriation General Hospital, in Adelaide, South Australia. Family functioning was assessed using the McMaster Family Assessment Device, and functional outcome was monitored with the competence scale of the Australian ADL Index. Longitudinal change in family functioning was observed in problem solving, family communication, role definition, behaviour control, and affective involvement. There were no significant differences between the family functioning ratings provided by patients and their spouses. It is important that consideration be given to means by which the increase in family dysfunction following stroke can be addressed.

Activities of Daily Living↗
PubMed1999

Generation and analysis of 25 Mb of genomic DNA from the pufferfish Fugu rubripes by sequence scanning.

We have generated and analyzed >50,000 shotgun clones from 1059 Fugu cosmid clones. All sequences have been minimally edited and searched against protein and DNA databases. These data are all displayed on a searchable, publicly available web site at. With an average of 50 reads per cosmid, this is virtually nonredundant sequence skimming, covering 30%-50% of each clone. This essentially random data set covers nearly 25 Mb (>6%) of the Fugu genome and forms the basis of a series of whole genome analyses which address questions regarding gene density and distribution in the Fugu genome and the similarity between Fugu and mammalian genes. The Fugu genome, with eight times less DNA but a similar gene repertoire, is ideally suited to this type of study because most cosmids contain more than one identifiable gene. General features of the genome are also discussed. We have made some estimation of the syntenic relationship between mammals and Fugu and looked at the efficacy of ORF prediction from short, unedited Fugu genomic sequences. Comparative DNA sequence analyses are an essential tool in the functional interpretation of complex vertebrate genomes. This project highlights the utility of using the Fugu genome in this kind of study.

Animals↗
PubMed1999

Psychological correlates of outcome following rehabilitation from stroke.

OBJECTIVES: To confirm, in a new sample, the value of our previously described procedure for identifying abnormal illness behaviour (AIB) in stroke rehabilitation patients, and to examine the relative effects of AIB, depression, family functioning, knowledge of stroke, and expectations of rehabilitation on long-term rehabilitation outcome. DESIGN: A longitudinal design, with assessments on admission to and discharge from rehabilitation, and six and twelve months after discharge. SETTING: The study was undertaken in the rehabilitation unit at Repatriation General Hospital, in Adelaide, South Australia. SUBJECTS: Sixty twelve-month stroke survivors, residing in a family environment, who had undergone an inpatient rehabilitation programme. MAIN OUTCOME MEASURES: AIB was assessed using the Illness Behaviour Questionnaire, depression with the Zung Self-Rating Depression Scale, family functioning with the McMaster Family Assessment Device, stroke knowledge with the Stroke Care Information Test, and expectations of rehabilitation with an open-ended question. Functional outcome was assessed with the competence and performance assessments of the Australian ADL Index, and lifestyle activities with the Frenchay Activities Index. RESULTS: Using our previously derived AIB classification rule, AIB cases scored poorly on functional, social and psychological indicators. Further, cluster analysis of discharge data replicated the rule for identifying patients with AIB. AIB was a strong predictor of functional competence and performance at rehabilitation discharge and both six and twelve months later, while depression was associated with an inactive lifestyle at both six and twelve months. Greater stroke knowledge and clearer expectations of rehabilitation were associated with better functional outcome at discharge. Family functioning was strongly associated with lifestyle activities and ADL performance at both six and twelve months. CONCLUSIONS: The procedure for identifying AIB in this rehabilitation environment appears to be robust. AIB was a key determinant of long-term functional disability, while depression was associated with poorer social functioning. Family functioning was an important determinant of social activities, and of the activities the patient actually does, rather than those the patient is capable of carrying out. Good stroke knowledge and clear expectations of rehabilitation were important determinants of rehabilitation success, and should be fostered to ensure a good rehabilitation outcome. Psychological factors are crucial in determining long-term outcomes after rehabilitation from stroke.

Activities of Daily Living↗
PubMed1998

The identification and characterization of microsatellites in the compact genome of the Japanese pufferfish, Fugu rubripes: perspectives in functional and comparative genomic analyses.

Fugu rubripes (Fugu) has one of the smallest recorded vertebrate genomes and is an economic tool for comparative DNA sequence analysis. Initial characterization of 128 kb of Fugu DNA attributed the compactness of this genome, in part, to a sparseness of repetitive DNA sequence compared with mammalian genomic sequences. This paper describes a new and comprehensive analysis in which 501 theoretically possible microsatellites with a repeat unit of one to six bases were used to query two orders of magnitude more Fugu DNA (i.e. 11.338 Mb). A total of 6042 microsatellites were identified and categorized. In decreasing order, the 20 most frequently occurring microsatellites are AC, A, C, AGG, AG, AGC, AAT, AAAT, ACAG, ACGC, ATCC, AAC, ATC, AGGG, AAAG, AAG, AAAC, AT, CCG and TTAGGG. The 20 most frequently occurring microsatellites represent 81.79% of all microsatellites identified. Our results indicate that one microsatellite occurs every 1.876 kb of DNA in Fugu, 11.55% of the microsatellites are detected in open reading frames that are predicted protein coding regions. With respect to the proportion of microsatellites present in open reading frames and the total abundance (bp) of all microsatellites, the genome of Fugu is similar to the genome of many other vertebrate species. Previous estimates performed indicate that approximately 1% of many vertebrate genomes are comprized of microsatellite sequences. However, many differences prevail in the abundance and frequency of the individual microsatellite classes. Many of the frequently occurring microsatellites in Fugu are known to code in other species for regions in proteins such as transcription factors, whilst others are associated with known functions, such as transcription factor binding sites and form part of promoter regions in DNA sequences of genes. Therefore, it is likely that such repeats in genomes have a role in the evolution of genes, regulation of gene expression and consequently the evolution of species.

Animals↗
PubMed1998

BDNF induction of tryptophan hydroxylase mRNA levels in the rat brain.

We have previously demonstrated an augmentation of serotonergic activity within various brain areas following infusion of brain-derived neurotrophic factor (BDNF) into the midbrain near the periaqueductal gray and dorsal and median raphe nuclei (PAG/DR). However, the mechanism of this BDNF-induced modulatory effect on serotonergic systems was unclear. The aim of the present work was to study the regulation of tryptophan hydroxylase (TPH) mRNA levels after chronic BDNF administration in vivo. TPH mRNA levels were measured using a quantitative competitive reverse transcription polymerase chain reaction (RT-PCR) assay. A significant increase in the expression of TPH mRNA (13-fold) was found within the PAG/DR as early as 24 hr after onset of BDNF infusion and was sustained throughout the duration of infusion (11 days). This was accompanied by increased serotonin (5-hydroxytryptamine, 5-HT) levels and decreased nociceptive responsiveness assessed by tail-flick latency. BDNF induction of TPH mRNA levels was also observed in a serotonergic cell line derived from raphe neurons, indicating that BDNF can directly regulate TPH mRNA levels. These results suggest that BDNF augments 5-HT synthesis in vivo by directly enhancing steady-state TPH mRNA levels, and subsequently leading to marked behavioral alterations.

Animals↗
PubMed1998

Sabcomeline (SB-202026), a functionally selective M1 receptor partial agonist, reverses delay-induced deficits in the T-maze.

Sabcomeline, (SB-202026 [R-(Z)-alpha-(methoxyimino)-1 -azabicyclo [2.2.2] octane-3-acetonitrile]), a functionally selective muscarinic M1 receptor partial agonist, was tested in rats trained to perform a delayed, reinforced alternation task in a T maze, a test of short-term spatial memory. For comparison the cholinesterase inhibitor tacrine (THA-9-amino- 1,2,3,4-tetrahydroaminoacridine) and the non-selective muscarinic receptor agonist RS86 (2-ethyl-8-methyl-2,8 diazospiro [4.5]-decane-1,3-dione hydrobromide) were also tested and all three compounds were also compared using a conditioned taste aversion (CTA) task. Sabcomeline (0.001-1.0 mg/kg i.p.) significantly reversed the T-maze choice accuracy deficit induced by a 20-s delay at 0.03 and 0.1 mg/kg. RS86 (0.1-3.0 mg/kg i.p.) reversed the deficit at 1.0 mg/kg and THA (0.1-3.0 mg/kg i.p.) had no effect at any dose. All three compounds induced conditioned taste aversion with minimum effective doses (MED) of 0.3, 1.0 and 3.0 mg/kg, respectively. The results show that sabcomeline reverses delay induced deficits in T-maze choice accuracy in a rewarded alternation task at doses approximately 10 times lower than those required to induce conditioned taste aversion. RS86 was equipotent in both tests. These data support the findings of clinical studies which have shown that SB-202026 provides significant symptomatic improvement in patients with probable Alzheimer's disease at doses which do not induce cholinergic side effects.

Animals↗
PubMed1998

Measurement of tryptophan hydroxylase mRNA levels by competitive RT-PCR.

Tryptophan hydroxylase (TPH) is the rate limiting enzyme in serotonin biosynthesis [D.G. Grahame-Smith, Tryptophan hydroxylation in brain, Biochem. Biophys. Res. Commun. 16 (1964) 586-592 [19]]. As such, the TPH gene is a likely target for modulation of serotonergic function, which has been associated with several psychiatric disorders [E.C. Azmitia, P.M. Whitaker-Azmitia, Awakening the sleeping giant: anatomy and plasticity of the brain serotonergic system, J. Clin. Psychiatry 52 (12, Suppl.) (1991) 4-16 [1]; R.P. Hart, R. Yang, L.A. Riley., T.L. Green, Post-transcriptional control of tryptophan hydroxylase gene expression in rat brain stem and pineal gland, Mol. Cell. Neurosci. 2 (1991) 71-77 [20]; M.J. Owens, C.B. Numeroff, Role of serotonin in the pathophysiology of depression: focus on the serotonin transporter, Clin. Chem. 40 (1994) 288-295 [24]]. Unfortunately, it has been technically difficult to measure TPH mRNA levels in central serotonergic neurons due to its low levels. For example, detection with ribonuclease protection assays requires pooling of 5-10 dissected brainstems [M.C. Darmon, B. Guibert, V. Leviel, M. Ehret, M. Maitre, J. Mallet, Sequence of two mRNAs encoding active rat tryptophan hydroxylase, J. Neurochem. 51 (1988) 312-316 [15]; B.L. Jacobs, E.C. Azmitia, Structure and function of the brain serotonin system, Physiol. Rev. 72 (1992) 165-229 [21]]. This protocol describes the use of competitive RT-PCR to measure TPH mRNA levels from rat brain. First described in 1988, competitive RT-PCR has become an accepted method of measuring RNA abundance [M. Clementi, S. Menzo, P. Bagnarelli, A. Manzin, A. Valenza, P.E. Varaldo, Quantitative PCR and RT-PCR in virology, PCR Methods Appl. 2 (1994) 191-196 [12]; N.C.P. Cross, Quantitative PCR techniques and applications, Br. J. Haematol. 89 (1995) 693-697 [14]; K.P. Foley, M.W. Leonard, J.D. Engel, Quantitation of RNA using the polymerase chain reaction, Trends Genet. 9 (1993) 380-385 [17]; P.D. Siebert, J.W. Larrick, Competitive PCR, Nature 359 (1992) 558 [27]]. Competitive RT-PCR uses co-amplification with a known quantity of an in vitro transcribed RNA which amplifies using the same primers and thus competes for reactants with the product of interest. As the two products amplify with the same efficiency, the relative abundance of the two amplification products remains constant, and thus can be used to determine initial tissue TPH mRNA levels [G. Gilliland, S. Perrin, K. Blanchard, H.F. Bunn, Analysis of cytokine mRNA and DNA: detection and quantitation by competitive polymerase chain reaction, Proc. Natl. Acad. Sci. U.S.A. 87 (1990) 2725-2729 [18]; A.M. Wang, M. V. Doyle, D.F. Mark, Quantitation of mRNA by the polymerase chain reaction, Proc. Natl. Acad. Sci. U.S.A. 86 (1989) 9717-9721 [31]]. We first demonstrate equivalent results between RNA slot blots and competitive RT-PCR using the CA77 thyroid C cell line [M.S. Clark, A. F. Russo, Tissue-specific glucocorticoid regulation of tryptophan hydroxylase mRNA levels, Mol. Brain Res. 48 (1997) 346-354 [9]]. We then describe the use of competitive RT-PCR to measure TPH mRNA levels in RNA isolated from rat brain poly-A+ RNA.

Animals↗
PubMed1998

Factors contributing to patient satisfaction with rehabilitation following stroke.

This study charted changes in patient satisfaction with their rehabilitative progress over time, and examined the relative contributions of several factors to satisfaction. Participants were assessed on admission to and discharge from rehabilitation, and six and 12 months after discharge. The study was undertaken in the rehabilitation unit at Repatriation General Hospital, in Adelaide, South Australia. Participants were 60 12-month stroke survivors who had undergone an inpatient rehabilitation programme. Satisfaction with progress in five areas of function was assessed using a five point rating scale. Functional outcome was assessed with the Australian ADL Index (competence and performance), lifestyle activities with the Frenchay Activities Index, knowledge of stroke with the Stroke Care Information Test, depression with the Zung Self-Rating Depression Scale, family functioning with the McMaster Family Assessment Device, and patients' expectations of rehabilitation by a qualitative assessment. Satisfaction with progress improved with time, particularly for dressing and washing, but for mobility declined after discharge. Satisfaction with progress was consistently influenced by the return to previous lifestyle activities, depression, family functioning, understanding of stroke, and clarity of expectations on admission to rehabilitation. It is important that the concept of successful rehabilitation acknowledges the perspective of the patient.

Activities of Daily Living↗
PubMed1998

Cytological and molecular characterization of repetitive DNA sequences of Solanum brevidens and Solanum tuberosum.

The chromosomal distribution, copy numbers, and nucleotide sequences were determined for four repetitive DNA clones, pSB1 and pSB7 of Solanum brevidens and pST3 and pST10 of Solanum tuberosum. Using fluorescence in situ hybridization (FISH), pSB1 and pSB7 were localized near the telomeres and in some centromeric and interstitial sites of S. brevidens chromosomes, but not in S. tuberosum chromosomes, after high stringency washes. The clone pST3 showed signals in the telomeric areas of a few chromosomes in S. tuberosum, but signals were not detected in S. brevidens. All three repeated sequences (pSB1, pSB7, and pST3) were detected in chromosomal areas that are typically known to contain tandemly repeated sequences. The S. tuberosum clone pST10 did not show signals in either species even at low stringency conditions. The estimated copy numbers of the four clones were 1500, 6750, 300, and 400 for pSB1, pSB7, pST3, and pST10, respectively, in the corresponding haploid genomes (S. brevidens and S. tuberosum). The inserts of the four clones pSB1, pSB7, pST3, and pST10 were 322, 167, 845 and 121 bp, respectively. After sequencing, no significant sequence homologies were found among the four clones. A homology search in sequence data bases showed that pSB7 has variable homology (78-100%) with another repetitive sequence of S. brevidens Sb4/2 depending on its subrepeat. It also showed some homology with one repeat of tomato (pLEG15) and one repeat of Solanum circaeifolium (pSC15).

Base Sequence↗
PubMed1998

The effects of depression and abnormal illness behaviour on outcome following rehabilitation from stroke.

OBJECTIVE: To examine the relative effects of depression and abnormal illness behaviour (AIB) on long-term rehabilitation outcome following stroke. DESIGN: A longitudinal design, with assessments on admission to and discharge from rehabilitation, and six and twelve months after discharge. SETTING: The study was undertaken in the rehabilitation unit at Repatriation General Hospital, in Adelaide, South Australia. SUBJECTS: Ninety-four twelve-month stroke survivors who had undergone an inpatient rehabilitation programme. MAIN OUTCOME MEASURES: AIB was assessed using the Illness Behaviour Questionnaire, and depression with the Zung Self-Rating Depression Scale. The General Health Questionnaire and a visual analogue mood scale were also used. Functional outcome was assessed with the competence and performance assessments of the Australian ADL Index, and lifestyle activities with the Frenchay Activities Index. RESULTS: Multivariate analysis of outcome controlled for age and stroke severity. AIB was a better predictor of functional competence and performance than either age or stroke severity, at rehabilitation discharge and both six and twelve months later. Depression was not related to functional competence and performance at any assessment, but was strongly predictive of an inactive lifestyle at both six and twelve months. By contrast, lifestyle activities were not related to AIB. CONCLUSIONS: Depression and AIB appear to have quite distinct effects on outcome. AIB emerged as a key determinant of long-term functional disability, while depression was associated with poorer social functioning. The early recognition and treatment of AIB and depression is important for the ultimate social and functional outcomes of stroke rehabilitation patients.

Activities of Daily Living↗
PubMed1998

Clinical applications of the Adelaide Activities Profile.

OBJECTIVE: The Adelaide Activities Profile (AAP) was developed from the Frenchay Activities Index, and has been shown to be a valid measure of the lifestyle activities of elderly people. The goals of the current study were to illustrate the value of applying the AAP in the clinical setting, and to demonstrate the relationship of the AAP to the use of formal services. DESIGN: Data were collected as part of the Australian Longitudinal Study of Ageing (ALSA). A community sample, stratified by age and sex, was chosen to be representative of the elderly population of Adelaide, South Australia. PARTICIPANTS: A sample of 1799 community-dwelling people aged 70 years and over. MEASURES: Lifestyle activities were assessed with the AAP, which provides measures of activity on four scales: domestic chores, household maintenance, service to others, and social activities. Participants were defined as users of formal services if they were active clients of any of the Domiciliary Care and Rehabilitation Services, Meals-on-Wheels, or the Royal District Nursing Society. RESULTS: Age and sex norms for the AAP were provided, and the clinical value of using these norms was illustrated by two contrasting case studies. Users of formal services had lower activity levels than nonusers for all AAP scales, particularly household maintenance and domestic chores. CONCLUSIONS: The AAP is a valuable addition to the standard battery of instruments used in the assessment of elderly people, and has clinical application as both a health outcome measure and an indicator of the need for intervention.

Activities of Daily Living↗
PubMed1998

Why aren't indices of relationship costs always negatively related to indices of relationship quality?

Many researchers have made the seemingly straightforward predictions that relationship rewards will be positively, and relationship costs will be negatively, associated with indices of relationship quality. Existing literature supports the hypothesis for rewards, but evidence regarding costs is mixed. Depending on the study, indices of costs have been observed to be negatively associated, unassociated, and even positively associated with relationship quality. We argue that the mixed results may have been due in part to past cost measures tapping three separate constructs: (a) a partner's intentional poor behavior directed at the participant, (b) negative things associated with the relationship (but not caused by the partner's intentional behavior), and (c) behaving in such a manner as to meet a partner's needs-something which often may involve performing undesirable activities, foregoing desired opportunities, or giving up money, time, or goods. We believe the first two types of costs should be negatively associated with relationship quality. However, we argue that the last type, because it involves adhering to communal norms (Clark & Mills, 1979,1993) will often tend to be either negligibly or even positively associated with relationship quality. In two studies the occurrence of these three categories of events in close relationships as well as the quality of those relationships were measured. The overall pattern of results supports our specific hypotheses as well as the general idea that a lack of conceptual clarity regarding "costs" has contributed to the current mixed nature of our literature on links between relationship costs and relationship quality.

Journal Article↗
PubMed1998

Knowledge of stroke in rehabilitation and community samples.

This study examined the stroke knowledge of 60 stroke rehabilitation patients, 46 spouses, 25 family members, and 103 people in the general community. Changes in stroke knowledge with time, and determinants of stroke knowledge, were also examined. Clinical participants were assessed on acute admission, admission to and discharge from rehabilitation, and 6 and 12 months after discharge. Community participants were assessed once. Instruments used were the Stroke Care Information Test, Australian ADL Index, Frenchay Activities Index, Illness Behaviour Questionnaire and Zung Self-rating Depression Scale. The stroke knowledge of all participants, particularly patients, was poor, but improved with time. Better-informed patients were younger, had milder strokes, were less depressed, were less likely to develop abnormal illness behaviour, and made a better functional recovery than patients with poorer knowledge. Structured information programmes are needed for stroke patients and their families. Improved community awareness of stroke may help the prospects for recovery and quality of life for people who have strokes.

Aged↗
PubMed1997

Design of [R-(Z)]-(+)-alpha-(methoxyimino)-1-azabicyclo[2.2.2]octane-3-acetonitri le (SB 202026), a functionally selective azabicyclic muscarinic M1 agonist incorporating the N-methoxy imidoyl nitrile group as a novel ester bioisostere.

Loss of cholinergic function is believed to be implicated in the cognitive decline associated with senile dementia of the Alzheimer type (SDAT). The disease is characterized by progressive loss of muscarinic receptors located on nerve terminals while postsynaptic muscarinic M1 receptors appear to remain largely intact. Muscarinic agonists acting directly on postsynaptic receptors offer the prospect of countering the cholinergic deficit in SDAT. This study describes a novel series of azabicyclic muscarinic agonists, which incorporate an oxime ether or modified oxime ether group as an ester bioisostere. Modification of the oxime ether function by the introduction of electron withdrawing groups led to the finding that the (Z)-N-methoxy imidoyl nitrile group serves as a stable methyl ester bioisostere. This culminated in the discovery of the quinuclidinyl N-methoxy imidoyl nitrile R-(+)-(Z)-5g which is a functionally selective muscarinic M1 partial agonist currently in phase III clinical trials for the treatment of SDAT. The selective profile of R-(+)-(Z)-5g can be rationalized in terms of the relative affinity of the compound at muscarinic receptor subtypes, the degree of agonist efficacy, and brain penetrancy.

Alzheimer Disease↗