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Biomedical subjects
Anne Johnson
Publications and source records attributed to Anne Johnson.
Defective N-acetylaspartate catabolism reduces brain acetate levels and myelin lipid synthesis in Canavan's disease.
Canavan's disease (CD) is a fatal, hereditary disorder of CNS development that has been linked to mutations in the gene for the enzyme aspartoacylase (ASPA) (EC 3.5.1.15). ASPA acts to hydrolyze N-acetylaspartate (NAA) into l-aspartate and acetate, but the connection between ASPA deficiency and the failure of proper CNS development is unclear. We hypothesize that one function of ASPA is to provide acetate for the increased lipid synthesis that occurs during postnatal CNS myelination. The gene encoding ASPA has been inactivated in the mouse model of CD, and here we show significant decreases in the synthesis of six classes of myelin-associated lipids, as well as reduced acetate levels, in the brains of these mice at the time of peak postnatal CNS myelination. Analysis of the lipid content of white matter from a human CD patient showed decreased cerebroside and sulfatide relative to normal white matter. These results demonstrate that myelin lipid synthesis is significantly compromised in CD and provide direct evidence that defective myelin synthesis, resulting from a deficiency of NAA-derived acetate, is involved in the pathogenesis of CD.
Acetic Acid↗
Unusual variants of Alexander's disease.
The purpose of this study was to describe unusual variants of Alexander's disease. We studied 10 patients who did not meet previously established magnetic resonance imaging (MRI) criteria for Alexander's disease, but for whom this diagnosis was considered because of Rosenthal fibers at histological examination or presence of some MRI features suggestive of Alexander's disease. Sequence analysis of the GFAP gene was performed. In eight patients, MRI results showed predominantly posterior fossa lesions, especially multiple tumor-like brainstem lesions. One patient had asymmetrical frontal white matter abnormalities and basal ganglia abnormalities. One patient (Patient 10) developed degeneration of the frontal white matter. In nine patients, a mutation was found that was concluded to be pathogenic, because the mutation was de novo (five patients), a known mutation was found (two patients), or assembly of the glial fibrillary acidic protein was abnormal in cultured cells (two patients). In Patient 10, a DNA variation was found that was also present in the patient's clinically unaffected father and was concluded to be a polymorphism. In conclusion, DNA diagnostics is warranted in patients who display MRI features suggestive of Alexander's disease, even if they do not meet the full set of previously established MRI criteria.
Adolescent↗
Long-stay views from the hospital bed: patient perspectives of organisation of care and impact of hospitalisation.
This study aimed to determine the perspectives of a group of patients categorised as "long-stay outliers" at a large South Australian metropolitan hospital about aspects of organisation of care and the perceived impact of long-term hospitalisation, Australia. Nineteen patients were interviewed using a semi-structured questionnaire. Eighty-nine percent of participants stated that they had no knowledge of how long they were to be in hospital. Forty-two percent indicated that they did not know when they would be discharged from hospital. This was of concern, especially considering the vulnerability of this patient group and the known benefits of patient involvement in decision making and the improvements this can make to health outcomes and early discharge. Participants indicated concern about sleep deprivation, diet, ability to return to paid employment, and missing their family as the main areas of impact of their long hospitalisation. Concerns about being discharged from hospital included: apprehension as to whether they were well enough to leave; the recurrence of infection; whether they would be able to sleep well when they got home; their recent loss of appetite and associated weight loss; mobility concerns; and what supports they would have when they were discharged home. All these issues require staff to be more patient and family-centred in their approach to preparing for discharge.
Adult↗
Benefits and barriers for registered nurses undertaking post-graduate diplomas in paediatric nursing.
This paper presents one aspect of a larger study identifying key influences on curriculum redesign and development of a post-graduate diploma in advanced clinical nursing. The focus is on paediatric intensive care and general paediatric streams. Data presented here relate to registered nurses' perceptions of benefits and barriers when undertaking this post-graduate diploma. As well as interviews and focus group discussions with a number of nurses, data were collected through a self-administered questionnaire, A total of 885 surveys were distributed to nurses working in paediatric areas in five hospitals in Victoria, Australia. Of these, 391 were completed (response rate 44%). One hundred and thirty (33%) had post-registration or post-graduate paediatric qualifications. Perceived benefits of undertaking the post-graduate diploma mainly related to an increase in knowledge and experience and improvement of employment opportunities. Perceived barriers mainly related to financial and professional issues such as cost of the course, loss of salary, the lack of direct remuneration on completion of the course and a lack of promotional opportunities. It was of concern that several nurses expressed a belief that paediatric qualifications were unnecessary and that many believed their employers did not value the qualification. Several recommendations are suggested to address the main barriers. These include more flexibility in the provision of such courses and opportunities for financial assistance.
Attitude of Health Personnel↗
Improving the quality of hospital services: how diverse groups of consumers prefer to be involved.
Consumer participation in hospitals is increasingly being advocated for as a way to contribute to improving safety and quality. This article reports on the results of a study conducted to investigate if, and how, a range of consumers would prefer to be involved in improving the quality of hospital services. Face-to-face interviews were conducted with 100 users of a hospital, telephone interviews were conducted with 2,005 members of the broader South Australian community, focus groups were conducted with 22 representatives of consumer and community groups and in-depth interviews conducted with four representatives who could not attend the focus groups. The results indicate that for users of the hospital and members of the broader community, there is a significant preference to be involved in more passive methods of participation that are initiated by the hospital, such as written and phone surveys. This is preferable to writing letters of complaint or compliment, participating in more active methods that require one-off commitment (focus groups and public planning forums) and ongoing commitment such as being members of working groups to address specific issues and hospital committees. In contrast, representatives of consumer and community groups have a strong preference to be involved in active methods of participation such as working groups to address specific issues and hospital committees. We found that there are considerable differences between age groups and educational attainment and preference for participation. If these issues are not taken into account, and a range of participation methods used, then there is the potential for some population groups to be excluded from having some input into improving the safety and quality of hospital services.
Adolescent↗
Androgen induced norepinephrine release from postganglionic neurons mediates accessory sex organ smooth muscle proliferation.
PURPOSE: Guinea pig seminal vesicle smooth muscle displays an initial androgen dependent, proliferative response during early puberty, followed by progression to an androgen resistant, amitotic state in adults. We determined the role of norepinephrine in androgen dependent pubertal proliferation and in the subsequent terminal differentiation of adult seminal vesicle smooth muscle. MATERIALS AND METHODS: Guinea pig seminal vesicle provided a suitable model since its unique anatomy allowed clean harvest of smooth muscle without epithelium. Norepinephrine release from postganglionic adrenergic nerve terminals in seminal vesicle smooth muscle was measured using several techniques. Prazosin sensitive electrical field stimulation of contractile responses qualitatively assessed norepinephrine release. Norepinephrine release was quantified directly in vitro from incubated seminal vesicle smooth muscle minces and indirectly ex vivo from intact tissue using the endogenous seminal vesicle smooth muscle concentration ratio of 3,4-dihydroxyphenylglycol-to-norepinephrine (Sigma Chemical Co., St. Louis, Missouri). Norepinephrine mediated seminal vesicle smooth muscle proliferation was assessed by the time course relationships of androgen induced norepinephrine release, protein kinase C activation-depletion and increases in total DNA, the impact of in vivo reserpine induced norepinephrine depletion on protein kinase C activation-depletion and the mitogenic response, and the alpha1-adrenoceptor mediated mitogenic response in cultured seminal vesicle smooth muscle cells. RESULTS: In prepubertal smooth muscle androgen induced norepinephrine release from postganglionic neurons. The effect was independent of preganglionic innervation. Increased norepinephrine release was concurrent with the onset of androgen induced protein kinase C activation-depletion and cellular proliferation. In vivo norepinephrine depletion to 1% or less of control values by chronic reserpine treatment selectively antagonized the androgen induced increases in smooth muscle DNA and protein kinase C down-regulation. Norepinephrine depletion by reserpine neither induced apoptosis nor altered cell number. Cell culture experiments demonstrated that alpha1-adrenoceptors mediated the proliferative response to norepinephrine. Together these findings indicate that increased norepinephrine release has an obligatory role in androgen dependent muscle cell proliferation during puberty. Terminally differentiated smooth muscle in adults was characterized by androgen resistance to elevated norepinephrine release and protein kinase C activation. CONCLUSIONS: Androgen induced norepinephrine release from postganglionic neurons in seminal vesicle smooth muscle mediated the proliferative response that occurs in early pubertal development. Normal uncoupling of elevated norepinephrine release and protein kinase C activation-depletion may represent a key event in the normal terminal differentiation of accessory sex organ smooth muscle in adults.
Animals↗
Regression of cervical intraepithelial neoplasia and loss of human papillomavirus (HPV) infection is associated with cell-mediated immune responses to an HPV type 16 E7 peptide.
Most human papillomavirus (HPV)-associated cervical intraepithelial neoplasia(CIN) lesions in normal women regress spontaneously, but a small number persist and may progress to invasive cancer. To evaluate the role of immunity to HPV and the outcome of CIN and associated HPV infection, we examined cell-mediated immune (CMI) responses to HPV 16 E6 and E7 peptides. One hundred thirty-six women with biopsy-confirmed CIN I or CIN II were followed for 1 year at 3 month intervals. Study subjects were 58% Hispanic, 36% African American, and 6% of other ethnicity, and were attending a municipal hospital colposcopy clinic. At each visit, cervical cytology and cervicovaginal lavage for HPV detection and typing was done, and blood was obtained for immunological studies. Lymphoproliferative CMI responses to HPV 16 E6 and E7 peptides were tested. An end point biopsy was done after the 1-year follow-up. The association between CMI responses to specific peptides and the outcome of disease was evaluated. CMI responses to E7 peptide (37-54) correlated significantly with regression of disease and with resolution of viral infection within 12 months. The protective effects of CMI to this peptide were not HPV type-specific. CMI responses to several other peptides also showed an association with regression, although not significant at present sample size. E7 peptide 37-54 contains one or more human T-cell epitopes. Identification and mapping of "protective" epitopes in the HPV E6 and E7 proteins could lead to the development of immunological assays to determine the risk of CIN and the development of immunotherapeutic protocols for the management of premalignant and malignant HPV-associated neoplasia and, ultimately, for the prevention of cancer.
Adult↗