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Biomedical subjects

T Koch

Publications and source records attributed to T Koch.

At least 55 records · Page 3Linked to original sources
PubMed2001

C-terminal splice variants of the mouse mu-opioid receptor differ in morphine-induced internalization and receptor resensitization.

The main analgesic effects of the opioid alkaloid morphine are mediated by the mu-opioid receptor. In contrast to endogenous opioid peptides, morphine activates the mu-opioid receptor without causing its rapid endocytosis. Recently, three novel C-terminal splice variants (MOR1C, MOR1D, and MOR1E) of the mouse mu-opioid receptor (MOR1) have been identified. In the present study, we show that these receptors differ substantially in their agonist-selective membrane trafficking. MOR1 and MOR1C stably expressed in human embryonic kidney 293 cells exhibited phosphorylation, internalization, and down-regulation in the presence of the opioid peptide [d-Ala(2),Me-Phe(4),Gly(5)-ol]enkephalin (DAMGO) but not in response to morphine. In contrast, MOR1D and MOR1E exhibited robust phosphorylation, internalization, and down-regulation in response to both DAMGO and morphine. DAMGO elicited a similar desensitization (during an 8-h exposure) and resensitization (during a 50-min drug-free interval) of all four mu-receptor splice variants. After morphine treatment, however, MOR1 and MOR1C showed a faster desensitization and no resensitization as compared with MOR1D and MOR1E. These results strongly reinforce the hypothesis that receptor phosphorylation and internalization are required for opioid receptor reactivation thus counteracting agonist-induced desensitization. Our findings also suggest a mechanism by which cell- and tissue-specific C-terminal splicing of the mu-opioid receptor may significantly modulate the development of tolerance to the various effects of morphine.

Alternative Splicing↗
PubMed2001

Clozapine-induced Fos-protein expression in rat forebrain regions: differential effects of adrenalectomy and corticosterone supplement.

Unlike classical antipsychotic drugs, clozapine activates the hypothalamo-pituitary-adrenal axis and induces a specific regional pattern of Fos-protein expression in the rat forebrain. Whether corticosterone plays a role in the clozapine-induced Fos response is the subject of this study. Some rats were adrenalectomized and in a number, including intact animals, a corticosterone pellet (100 mg s.c.) was implanted; after 1 week, a single dose of clozapine (20 mg kg(-1) i.p.) was administered. The clozapine-induced Fos response was not affected by adrenalectomy, apart from the nucleus accumbens shell, the subfornical organ and the supraoptic nucleus; there was an increased response in the nucleus accumbens shell, while other regions showed less Fos immunoreactivity. Implantation of the corticosterone pellet in both sham-operated and adrenalectomized animals, reduced the clozapine-induced Fos responses strongly in the hypothalamic paraventricular nucleus, the subfornical organ and possibly in the prefrontal cortex; in the supraoptic nucleus, this effect was seen only in intact animals. The effect of clozapine on plasma corticosterone levels was also diminished by supplemental corticosterone treatment. These results imply that the effects of clozapine are partially dependent upon hypothalamo-pituitary-adrenal axis integrity and activation. The efficacy of clozapine in the treatment of polydipsia and hyponatremia in chronic psychiatric patients may involve clozapine-mediated activation of the cellular activity in the subfornical organ.

Adrenalectomy↗
PubMed2001

Stopped-flow kinetics of locked nucleic acid (LNA)-oligonucleotide duplex formation: studies of LNA-DNA and DNA-DNA interactions.

The locked nucleic acid (LNA) monomer is a conformationally restricted nucleotide analogue with an extra 2'-O,4'-C-methylene bridge added to the ribose ring. Oligonucleotides that contain LNA monomers have shown greatly enhanced thermal stability when hybridized to complementary DNA and RNA and are considered most promising candidates for efficient recognition of a given mixed sequence in a nucleic acid duplex and as an antisense molecule. Here the kinetics and thermodynamics of a series of oligonucleotide duplex formations of DNA-DNA and DNA-LNA octamers were studied using stopped-flow absorption measurements at 25 degrees C and melting curves. The reactions of the DNA octamer 5'-CAGGAGCA-3' with its complementary DNA octamer 5'-TGCTCCTG-3', and with the LNA octamers 5'-T(L)GCTCCTG-3' (LNA-1), 5'-T(L)GCT(L)CCTG-3' (LNA-2) and 5'-T(L)GCT(L)CCT(L)G-3'(LNA-3), containing respectively one, two or three thymidine 2'-O,4'-C-methylene-(D-ribofuranosyl) nucleotide monomers, designated T(L), were studied. In all cases were seen fast second-order association reactions with k(obs)=2x10(7) M(-1)s(-1). At 25 degrees C the dissociation constants of the duplexes obtained from melting curves were: DNA-DNA, 10 nM; DNA-LNA-1, 20 nM; DNA-LNA-2, 2 nM; and DNA-LNA-3, 0.3 nM; thus the greatly enhanced duplex stability induced by LNA is confirmed. Since the association rates were all equal this increase in stability is due to slower rates of dissociation of the complexes.

DNA↗
PubMed2001

Extrafloral nectar production of the ant-associated plant, Macaranga tanarius, is an induced, indirect, defensive response elicited by jasmonic acid.

Plant species in at least 66 families produce extrafloral nectar (EFN) on their leaves or shoots and therewith attract predators and parasitoids, such as ants and wasps, which in turn defend them against herbivores. We investigated whether EFN secretion is induced by herbivory and/or artificial damage, and thus can be regarded as an induced defensive response. In addition, we studied the underlying signaling pathway. EFN secretion by field-grown Macaranga tanarius increased after herbivory, artificial leaf damage, and exogenous jasmonic acid (JA) application. Artificial damage strongly enhanced endogenous JA concentrations. The response in EFN production to artificial damage was much less pronounced in those leaves that were treated with phenidone to inhibit endogenous JA synthesis. Quantitative dose-response relations were found between the increase in nectar production and both the intensity of leaf damage and the amounts of exogenously applied JA. The amount of endogenously produced JA was positively correlated with the intensity of leaf damage. Increased numbers of defending insects and decreased numbers of herbivores were observed on leaves after inducing EFN production by exogenous JA treatment. Over 6 weeks, repeatedly applied JA or artificial damage resulted in a ten-fold reduction in herbivory. These results demonstrate that EFN production represents an alternative mechanism for induced, indirect defensive plant responses that are mediated via the octadecanoid signal transduction cascade.

Animals↗
PubMed2001

PNA synthesis using a novel Boc/acyl protecting group strategy.

The synthesis of novel Boc/acyl protected monomers for the synthesis of peptide nucleic acid (PNA) is described. The oligomerization protocol using these new monomers has been optimized with regard to coupling reagents. The use of base-labile acyl protecting groups at the exocyclic amines of the heterocyclic bases (isobutyryl for guanine and benzoyl for adenine and cytosine) and a PAM-linked solid support offers an attractive alternative to the present procedures used in PNA synthesis. This strategy has been applied for the synthesis of a test 17mer PNA on both control pore glass (CPG) and a polystyrene MBHA support and was used in the preparation of PNA-DNA chimeras.

Biochemistry↗
PubMed2001

[Cellular dysfunction in the pathogenesis of organ failure. New insights from molecular and cell biology].

Multiple organ failure remains the major cause of death in critically ill patients. In view of therapeutic strategies, current research activities focus on the cellular response to different kinds of cellular stress (hypoxia, oxidative damage and mechanical distress) in the pathogenic sequelae of organ failure. The cellular stress reactions are characterized by induction of adaptive programs of gene expression (e.g. acute phase proteins, heat shock proteins, hypoxia-associated proteins) to protect the cells from energy depletion and cell death. Generally, the mitochondria are early indicators of cellular stress showing a loss of cytochrome c and a breakdown of the transmembrane potential. Shortage of ATP and decrease of pH can be observed in the cytoplasm which leads to a disintegration of the cytoskeleton. As a consequence, the cell becomes spherical and separates from the surrounding cells. Depending on the acuity of the stressor, the cell dies due to necrosis or apoptosis. Dysregulation of the balance of apoptosis and necrosis in different organs seems to be an important mechanism in the development of organ failure. New insights into the cellular mechanisms during organ dysfunction promote the development of new diagnostic (e.g., optical and spectroscopic) and pharmacological tools leading to a better prevention and therapy of organ failure.

Animals↗
PubMed2001

Effects of inhalation of perfluorocarbon aerosol on oxygenation and pulmonary function compared to PGI2 inhalation in a sheep model of oleic acid-induced lung injury.

OBJECTIVE: To evaluate the effects of PFC aerosol compared to PGI2 aerosol and NaCl aerosol on gas exchange and lung mechanics in oleic acid-induced acute lung injury. DESIGN: A prospective, controlled, randomised, in vivo animal laboratory study. SETTING: Research laboratory at an university hospital. SUBJECTS: Twenty one (n = 21) adult sheep of either gender weighing 26.8+/-6.4 kg. INTERVENTIONS: The animals were randomised to three groups: PFC aerosol (perfluorooctane), PFC group; prostacyclin aerosol (Flolan), PGI2 group; and NaCl aerosol (0.9% sodium chloride solution), control group. After induction of anaesthesia and placement of vascular catheters, lung injury was induced with 0.12 ml x kg(-1) oleic acid. Aerosols were continuously administered for 2 h using a jet nebuliser. Gas exchange, pulmonary mechanic, and haemodynamic parameters were obtained at regular intervals. MEASUREMENTS AND MAIN RESULTS: PFC aerosol increased oxygenation (PaO2) 15 min after the initiation of treatment up to 120 min (P < 0.05). Transpulmonary shunt improved in the PFC group (P < 0.05) while it did not change in the two other groups. PFC aerosol reduced maximum airway pressure (Pmax) (median) significantly from (median) 38 mbar to 32 mbar (P < 0.05). Static compliance improved significantly in the PFC group (P < 0.05). CONCLUSION: The inhalation of a PFC aerosol led to a significant improvement in pulmonary mechanics and gas exchange, which was not observed in the other two groups. These data suggest that a small dose of perfluorocarbon will have beneficial effects on gas exchange and respiratory mechanics. Therefore, the non-invasive aerosol application technique seems to be a reasonable alternative to administer perfluorocarbons in severe lung injury.

Aerosols↗
PubMed2001

Client relevant care and quality of life: the trial of a Client Generated Index (CGI) tool for community nursing.

Community nursing organisations worldwide seek optimal ways to ensure adequate measurement of health outcomes for the client following nursing care, and to facilitate a consumer focus. This article presents a trial of the Client Generated Index (CGI) tool that subjectively assesses and measures the quality of life outcomes pertaining to a client's health status, whilst also facilitating individualised care. Sixty district nursing clients participated in the trial, which ascertained that the CGI tool effectively directs the client to list, grade and prioritise personally relevant quality of life issues. Consequently, this tool is being incorporated into client admission and discharge assessment within the organisation.

Activities of Daily Living↗
PubMed2001

Future states: the axioms underlying prospective, future-oriented, health planning instruments.

Proscriptive planning exercises are critical to and generally accepted as integral to health planning at varying scales. These require specific instruments designed to predict future actions on the basis of present knowledge. At the macro-level of health economics, for example, a number of future-oriented Quality of Life Instruments (QL) are commonly employed. At the level of individual decision making, on the other hand, Advance Directives (AD's) are advanced as a means by which healthy individuals can assure their wishes will be carried out if at some future point they are incapacitated. As proscriptive tools, both instrument classes appear to share an axiomatic set whose individual parts have not been rigorously considered. This paper attempts to first identify and then consider a set of five axioms underlying future oriented health planning instruments. These axioms are then critiqued using data from a pre-test survey designed specifically to address their assumptions. Results appear to challenge the validity of the axioms underlying the proscriptive planning instruments.

Advance Directives↗
PubMed2001

GIS approaches to the problem of disease clusters: a brief commentary.

This commentary considers issues raised in a recent article on GIS-based approaches to modeling disease clusters. 'Modeling exposure opportunities' (Sabel, Gatrell & Löytönen et al., 2000. Social Science and Medicine, 50, 1121-37) and the general problem of mapping disease clusters. It notes that the authors' advocate a fundamentally statistical approach, Kerneling estimation, to map the occurrence of a specific illness whose etiology is unknown. Epidemiologists, ironically, have advocated a fundamentally cartographic solution, the cartogram, in addressing the general problem of disease clusters. The advantages and limits of both approaches are reviewed and the potential for their comparison in a single study suggested. Most importantly, perhaps, the commentary seeks to join the epidemiological and medical geographic literatures as they pertain to this analytic problem and medical cartography's potential (GIS-based or traditional) to understand disease etiology.

Algorithms↗
PubMed2001

Women's experiences of 'being diagnosed' with a long-term illness.

AIMS: In this paper we share women's storied accounts of 'being diagnosed' with a long-term illness. The purpose of the paper is to raise awareness of health professionals that receiving a medical diagnosis is a potentially calamitous event, challenging self-identity. BACKGROUND: The three authors were involved in three separate inquiries which explored women's experiences of living with illness. The authors realized that 'being diagnosed' was a common memorable event for the women across the inquiries. The literature around receiving a diagnosis was scarce. DESIGN: This paper is the result of secondary analysis of data from three different projects where we researched women living with long-term illness. In this paper, we focus on the experience of 'being diagnosed' as we share and show women's perceptions of receiving a medical diagnosis. FINDINGS: Receiving a medical diagnosis of a long-term illness was a memorable event in the women's lives. Many women felt alone with their illness, often without adequate information to find meaning in the relationship between their familiar self and their new identity as a woman living with illness. They felt vulnerable and lost as they tried to understand the meanings and consequences that the diagnosis held for their present and their future. Informational needs may be specific and individual. For many, receipt of a diagnostic label was momentous and should not be underestimated, despite the initial feeling of chaos, many women felt validated. CONCLUSION: Receiving a medical diagnosis is one event where health care professionals could be on standby. It is important to take the woman's articulation of the event seriously. Open, genuine communication, with willingness on behalf of the health professional to listen would be affirming for women who are coming to terms with the diagnosis of a chronic illness.

Adaptation, Psychological↗
PubMed2001

Constructions of sexuality for midlife women living with chronic illness.

AIM: In this paper, we reveal constructions of sexuality that were articulated by women who participated in an inquiry which aimed to understand the experiences of midlife women who live with chronic illness. The aim of this paper is to illuminate sexuality as an important health issue for women living with chronic illness and to offer ways that nurses may acknowledge and facilitate sexuality issues for women. BACKGROUND: The first author, as part of her doctoral study, corresponded with 81 women living with chronic illness. The participatory inquiry was framed by feminist principles and enabled women to anonymously share their experiences and collaborate in the direction of the research. During the analysis phase of the research, it became evident that illness had altered the way in which women conceptualized sexuality. DESIGN: The three authors performed secondary analysis of the original data set in order to re-examine the impact that chronic illness had on the sexuality of midlife women who live with chronic illness. Whilst we acknowledge that sexuality has multiple meanings, in this paper we describe the way in which women themselves have constructed and articulated their sexuality. FINDINGS: We found that sexuality incorporated women's desires, appearance, sexual feelings and expression and imposed on aspects of their lives that they had not needed to acknowledge before illness intruded. Three concerns are discussed; the changing body, meeting the needs of others and communicating sexuality. CONCLUSIONS: This paper reveals that issues of sexuality are an important health concern for women who live with long-term illness and should be acknowledged in sensitive and responsive health practices. The paper concludes that it is important for nurses to provide women opportunity for open and genuine communications about sexuality. In this way, a foundation of acceptance for the whole person is established which provides women permission to ask questions and seek assistance with sexuality issues.

Adult↗
PubMed2001

Chronic illness: reflections on a community-based action research programme.

AIM: The purpose of this paper is to describe the birth of a research culture in a community nursing service, and the development and implementation of an action research programme that focuses on understanding the experiences of living with chronic illness. BACKGROUND: Approximately 70% of the clients of our community nursing practice in South Australia live with chronic illness. Our research interest has focused on how community nurses can assist people living with chronic conditions to live 'well'. In this paper we describe the way in which we have applied the principles of participatory action research (PAR) when working with women who live with multiple sclerosis (MS) and urinary incontinence. We then draw on elements of PAR research with men who live with MS and men and women who live with type 2 diabetes. In total, we have convened eight PAR groups researching with people who live in the community with chronic illness and this work constitutes our chronic illness research programme. DESIGN: The PAR philosophy is based on the principles of democratic, equitable, liberating and life enhancing relations within a research process, and is operationalized in cycles of: look, think and act. In these collaborative inquiries the researchers have facilitated participants to reflect on how illness affects their lives, to tell their own story, make connections, plan action and help them negotiate the rites of passage. We select two areas for discussion: methodological issues in the application of PAR principles and our tentative findings from the chronic illness research programme. FINDINGS: We assert that the facilitator's skill in managing group dynamics is crucial to the life and outcome of the project. Change can occur as a result of action at an individual level, with improved self-management of chronic illness, or at a collective level where the PAR group instigates larger reform strategies. In terms of tentative findings, men and women living with a chronic illness appear to be involved in an ongoing process of transition toward incorporating the illness into their lives. Although we have not yet identified specific events, we have noted that there are critical turning points in the illness transition experience. Participants feel validated in telling their story of living with a chronic illness. Story telling may be the turning point that enhances the lives of all those who participate. CONCLUSION: If health care professionals can understand the process that facilitates people to move toward incorporating chronic illness into their lives, we can make a substantial contribution to enhance their chronic disease self care management.

Chronic Disease↗
PubMed2001

Evaluating a community nursing service: listening to the voices of clients with an intellectual disability and/or their proxies.

The aim of this study was to evaluate a specialist nursing service programme for people with an intellectual disability residing in the community. It is important to correct the imbalance in the literature that has neglected the voices of the clients themselves or denied expression by their proxies. The aim of the study was to gain a better understanding of matters of importance for clients and their families and to involve them in the evaluation of a service that directly affects their care. Only three clients were able to participate; however, 17 parents (next of kin) agreed to be interviewed. In-depth interviews were audio-taped, transcribed and analysed relating to the questions asked and were checked against the domains of the nursing practice in the disability area: continuity of care, advanced nursing practice, education and credentialling, personal and professional attributes, primary health care, and normalization. The findings confirm the high regard in which the programme is held. Service evaluation is crucial in providing evidence for programme funders. The favourable outcome of this evaluation meant that the programme gained funding for another few years.

Adaptation, Psychological↗
PubMed2001

Towards the eradication of head lice: literature review and research agenda.

Head lice infestation is a public health issue. In the effort to compile an evidence-base about the physiology, detection, treatment, effects and management strategies of head lice infestations we reviewed current literature. This literature signalled significant evidence gaps and these gaps provide incentives for further research. Our conclusions from the literature are that parents of children are responsible for head lice detection and treatment but have varying access to advice about how best to treat this condition. Concern is exacerbated by misconceptions surrounding the circumstances of infestation. Head lice are a low priority for health professionals in Australia, whereas parents and teachers believe the problem necessitates greater attention. It is important to provide a unified evidence-based approach to good information. It is timely for health care professionals to re-examine and prioritize this public health issue. They should research and work collaboratively towards the eradication of head lice.

Animals↗
PubMed2001

'The real stuff': implications for nursing of assessing and measuring a terminally ill person's quality of life.

Two quality of life (QoL) assessment and measurement tools, the Client Generated Index (CGI) and the McGill Quality of Life (MQOL) questionnaires, were trialled within district nursing palliative care to test usefulness and feasibility for holistic intervention selection, individualized palliative care planning, and measurement of the quality of dying. The specific focus of this paper is to discuss the less tangible outcomes of the trial, which illuminate the partly 'hidden' value and nature of clinical nursing. These outcomes include awareness that the use of such tools may: by actual administration of the tool be, in and of itself, a therapeutic nursing action; focus on 'the real stuff from the client's perspective, that which matters most to the terminally ill client, but may not be classically considered as prompting nursing intervention; and facilitate 'the real stuff' of nursing, perhaps known but not usually articulated by nurses, and which usually does not feature on care plans nor in time allocation schedules.

Adult↗
PubMed2001

Breaking the silence: women living with multiple sclerosis and urinary incontinence.

This study examined women's understandings of living with multiple sclerosis (MS) and urinary incontinence and the challenges they have encountered in their day-to-day lives. As health-care professionals, we aimed to understand how people living with MS manage urinary incontinence. This paper reports the findings from a Participatory Action Research (PAR) group with four women, the researcher and two Continence Nurse Advisors (CNAs). The group met on five occasions between March and June 1999. The women's stories held personal and gendered meanings about living with MS and urinary incontinence. Four themes were derived from the transcripts: maintaining control; seeking understanding; avoiding shame; and good and bad days. The women and the CNAs benefited from an exchange of knowledge about living with MS and incontinence. The CNAs became sensitive to the women's experience and have been able to incorporate these understandings into their practice. By sharing our research we hope the findings may be more widely incorporated into sensitive health practice.

Adaptation, Psychological↗