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Biomedical subjects

K Manley

Publications and source records attributed to K Manley.

At least 19 recordsLinked to original sources
PubMed1999

Instability of the CAG repeat in immortalized fibroblast cell cultures from Huntington's disease transgenic mice.

Huntington's Disease transgenic mice were used for an exploration into the stability of a trinucleotide repeat. The brain shows heterogeneous somatic instability that increases quantitatively with age. To test somatic CAG-repeat alterations during long-term culture, DNA was extracted from transgenic tissue, primary fibroblasts, and SV40-immortalized fibroblasts at intervals of approximately 100 cell doublings. In fibroblasts derived from an adult mouse, there was an initial short truncation of the repeat, followed by an emerging population of cells showing continuous slow expansion. After 15 months in continuous culture (approximately 600 cell doublings following transformation) the major CAG peak has increased from 155 to approximately 170 triplets. This in vitro system can now be used to assay factors that affect instability.

Animals↗
PubMed1999

An early-onset congenic strain of the motor neuron degeneration (mnd) mouse.

The mouse mutant motor neuron degeneration (mnd/mnd) has been proposed as a model of neuronal ceroid lipofuscinosis (NCL) on the basis of widespread abnormal accumulating lipopigment and neuronal and retinal degeneration. Clinically, the mutant on a C57Bl/6 genetic background shows a progressive motor abnormality starting by 6 months of age, with death prior to 12 months. When mnd is outcrossed to the AKR/J genetic background, ca. 40% of the mnd/mnd F2 progeny show early onset (onset by 4.5-5 months and death by 7 months). A congenic strain of mnd has now been produced by eight generations of backcross onto the AKR background. Mice on this background show average onset at 4 months, and most are moribund prior to 5.5 months. The early onset appears to correlate with levels of abnormal accumulating material, and should prove useful in elucidating NCL neurodegenerative mechanisms.

Age Factors↗
PubMed1999

Msh2 deficiency prevents in vivo somatic instability of the CAG repeat in Huntington disease transgenic mice.

Huntington disease (HD), an autosomal dominant, progressive neurodegenerative disorder, is caused by an expanded CAG repeat sequence leading to an increase in the number of glutamine residues in the encoded protein. The normal CAG repeat range is 5-36, whereas 38 or more repeats are found in the diseased state; the severity of disease is roughly proportional to the number of CAG repeats. HD shows anticipation, in which subsequent generations display earlier disease onsets due to intergenerational repeat expansion. For longer repeat lengths, somatic instability of the repeat size has been observed both in human cases at autopsy and in transgenic mouse models containing either a genomic fragment of human HD exon 1 (ref. 9) or an expanded repeat inserted into the endogenous mouse gene Hdh (ref. 10). With increasing repeat number, the protein changes conformation and becomes increasingly prone to aggregation, suggesting important functional correlations between repeat length and pathology. Because dinucleotide repeat instability is known to increase when the mismatch repair enzyme MSH2 is missing, we examined instability of the HD CAG repeat by crossing transgenic mice carrying exon 1 of human HD (ref. 16) with Msh2-/- mice. Our results show that Msh2 is required for somatic instability of the CAG repeat.

Animals↗
PubMed1999

Towards practice development--a vision in reality or a reality without vision?

This paper describes the development of a conceptual framework for practice development. Drawing on the authors' combined experiences of facilitating developments in practice, a conceptual framework is proposed. It is argued that much practice development in health care today lacks a systematic approach and is often undertaken by individual practitioners who are poorly prepared for their roles. A short history of practice development is outlined to contextualize current development activities. The proposed framework is located in a critical social science philosophy and it is suggested that such a philosophy enables individual growth and development, empowerment of practitioners and the generation of cultural change that sustains continuous growth and innovation in practice. An example of the framework in use is described and recommendations proposed to enable organizations to embrace a systematic approach to practice development.

Clinical Competence↗
PubMed1997

A conceptual framework for advanced practice: an action research project operationalizing an advanced practitioner/consultant nurse role.

A preliminary conceptual framework for an advanced practice/consultant nurse role is presented which links the role to its context and outcomes. The conceptual framework was developed in the process of analysing data from a 3-year action research study involving the operationalization of an advanced practice/consultant nurse role in a Nursing Development Unit. The skills and knowledge base of consultancy, underpinned by a strong nursing foundation, augmented by strong leadership and combined with the educator and researcher functions, are presented as the attributes of the advanced practitioner/consultant nurse. The facilitation of a transformational culture is highlighted as central to the skills and processes used within the role. Implications for the preparation and accreditation of the advanced practitioner/consultant nurse are highlighted.

Certification↗
PubMed1997

Nursing staff's perceptions and experiences of primary nursing practice in intensive care 4 years on.

This study explores the perceptions of staff who have been practising primary nursing for more than 4 years in intensive care. It considers what primary nursing is, what its benefits, disadvantages, and role impact are and other issues within an intensive care setting from the staff's perceptions and experiences. Although many of the perceived advantages and disadvantages are similar to experiences from other areas of nursing, there are some differences. The differences seem to relate to the way primary nursing is practised within the research setting-each primary nurse works with the same small team of associates, which is perceived as providing added benefits in terms of personal support and development of junior staff. The changes in role are seen to reflect other models in the literature which focus on becoming more patient centred and on working therapeutically. A number of future issues are addressed.

Attitude of Health Personnel↗
PubMed1996

The development of swimming behavior in the neurological mutant weaver mouse.

Weaver (wv/wv) mice have well-specified ontogenetic defects in both the cerebellum and striatum, but have not previously been evaluated systematically for patterns of motor development. In this study, the effects of the weaver mutation were evaluated through an examination of swimming behavior over the first 3 postnatal weeks. Detailed movement analyses of individual limb movements as well as interlimb coordination were used to evaluate the effects of the weaver mutation. Weaver mutant mice displayed a developmental lag in terms of swimming style relative to controls. They also displayed a generalized slowness in limb movements during the swim, which correlated with the developmental onset of use of a particular limb during the swim. However, basic motor patterns in weaver swimming continue to exhibit good overall coordination through the 3rd postnatal week, even though locomotor ataxia has become pronounced by this time. Our results indicate that specific and limited alterations in movement can be traced to very early in development (postnatal Day 3) in weaver mutant mice, a time at which the earliest biochemical and neuroanatomical deficits in these animals have been established. Our results also emphasize the need for systematic contextual analyses of movement to understand interlocking processes both in movement ontogeny and its disorders.

Animals↗
PubMed1993

Regulation of pelvic patch water flow in Bufo marinus: role of bladder volume and ANG II.

This report examines the importance of bladder volume in regulating cutaneous water uptake (Jv, cm3.cm-2.s-1 x 10(-7)) across the ventral pelvic patch and examines the role of angiotensin II (ANG II) and circulation as the regulatory mechanism. Jv in empty-bladder Bufo marinus (bladder volume 3.89 +/- 1.49%, n = 7) was 1,671 +/- 68 (n = 7). Injection of Ringer solution into the bladder (12.8 +/- 2.2%, n = 7) decreased Jv to 1,025 +/- 202 (n = 7). ANG II injected into toads with filled bladders increased Jv in a dose-dependent manner. At 5 micrograms/100 g toad Jv increased by 136 +/- 63 (n = 6), at 50 micrograms/100 g toad by 432 +/- 82 (n = 7), and at 200 micrograms/100 g toad by 620 +/- 142 (n = 5). Saralasin (200 micrograms/100 g toad) completely inhibited the response to ANG II (50 micrograms/100 g toad) and at 1 mg/100 g toad decreased Jv in empty-bladder toads. These experiments indicate that 1) bladder volume participates in the regulation of Jv in the ventral pelvic patch; 2) ANG II increases the Jv in toads with full bladders; 3) saralasin inhibits the high Jv in empty bladder toads; 4) the high Jv, associated with an empty bladder, requires an intact circulation to be maintained; 5) without an intact circulation, the high water flow associated with an empty bladder causes the Na+ content of the tissue in the ventral patch to be reduced; and 6) ANG II causes only a minimal increases in water permeability in the isolated pelvic patch skin.

Angiotensin II↗
PubMed1989

A follow-up study of three hepatitis B virus markers in personnel from the Canadian Armed Forces.

Prevalence rates for three hepatitis B virus (HBV) markers in two groups of personnel within the Canadian Armed forces (1848 incoming recruits and 210 crew members from a destroyer) were determined. Blood specimens for analysis were provided twice. The initial prevalence rates fell at the lower end of the spectrum when compared with those found in United States military personnel, Canadian military health personnel, and certain Canadian civilian populations. Eleven recruits and one destroyer crew member seroconverted for at least one of the markers between the first and the second testing. Their serological profiles are discussed in detail. No transmission of HBV between individuals in the group of recruits studied was established. However, evidence was found for a probable limited transmission of HBV between two crew members of HMCS Margaree. These findings combined with the high cost of the hepatitis B vaccine indicate that mass immunization for HBV in the Canadian Forces population cannot be justified on the basis of this study.

Adolescent↗
PubMed1989

Hepatitis A: a serological study in the Canadian Armed Forces.

Sera were collected from 3958 Canadian Forces personnel, including recruits, personnel posted to bases in Canada and on rotation with United Nations Peacekeeping forces, and the crew of a Canadian destroyer. All sera were tested for the presence of anti-hepatitis A antibodies by a competitive radioimmunoassay. The overall prevalence of anti-hepatitis A antibodies was found to be 23.5% (3.2% to 40.0%). The incidence of viral hepatitis A, as measured by seroconversion in paired sera, was found to be 0.17% (0.01% to 1.42%). The study results support the existence of a direct relationship between increasing age and an increased prevalence of anti-hepatitis A antibodies.

Adolescent↗
PubMedDate not supplied

The effect of sodium intake on blood pressure related to the age of the patients.

1. Sodium intake was varied in 182 normotensive volunteers. 2. systolic blood pressure rose by 3.3 (s.e.m. = 0.9) mmHg supine, 2.8 (s.e.m. = 0.7) mmHg erect. 3. Diastolic blood pressure rose by 2.7 (s.e.m. = 0.8) mmHg supine, 2.6 (s.e.m. = 0.8) mmHg erect. 4. In people over 50 y the rise was 12.4/8.1 mmHg (supine) and 9.1/7.1 mmHg (erect). 5. Blood pressure rose as sodium intake increased. Most of the rise was in the older patients but about 25% of younger patients were sensitive to sodium.

Adolescent↗