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Biomedical subjects

D Ritchie

Publications and source records attributed to D Ritchie.

At least 19 recordsLinked to original sources
PubMed2000

Follicular dendritic cells in scrapie pathogenesis.

Scrapie pathogenesis was studied in chimaeric mice that carried the prion protein (PrP) gene only in particular cells of the immune system. These mice were produced by grafting bone marrow from PrP expressing donors into PrP deficient recipients and vice versa. As follicular dendritic cells are not replaced significantly from the bone marrow in adult mice, this procedure resulted in a mismatch in PrP genotype between these cells and bone marrow derived cells such as lymphocytes. Using these models we obtained strong evidence that follicular dendritic cells produced high levels of the normal form of PrP in uninfected mice. Furthermore, the replication of a mouse-passaged scrapie strain in the spleen depended only on the presence of PrP expressing follicular dendritic cells. PrP expression by lymphocytes or other bone marrow derived cells had no influence on replication in spleen or on neuroinvasion in these models. These results indicate that the follicular dendritic cell is a potential target for prophylactic or therapeutic intervention in transmissible spongiform encephalopathies.

Animals↗
PubMed1999

Conflicting MRI signals from gliosis and neuronal vacuolation in prion diseases.

Magnetic resonance imaging (MRI) has given inconsistent results when used as a non-invasive diagnostic tool for Creutzfeldt-Jakob disease (CJD). In order to understand this finding, we studied a hamster model of scrapie by in vivo MRI and histopathology. Vacuolation of neurones/neuropil and gliosis were found to correlate with hypo-intense and hyper-intense changes in the conventional T2-weighted MR images, respectively. These opposing effects were shown to give rise to normal images of a scrapie-affected brain undergoing severe neurodegeneration, and may underlie the variability of previous CJD MRI data.

Animals↗
PubMed1998

Management of health system reform: a view of changes within New Zealand.

This paper reports on the context and process of health system reform in New Zealand. The study is based on interviews conducted with 31 managers from three Crown Health Enterprises (publicly funded hospital-based health care organizations). A number of countries with publicly funded health services (e.g., UK, Australia and New Zealand) have sought to shift from the traditional 'passive' health management style (using transactional management skills to balance historically-based expenditure budgets) to 'active' transformational leadership styles that reflect a stronger 'private sector' orientation (requiring active management of resources--including a return on 'capital' investment, identification of costs and returns on 'product lines', 'marketing' a 'product mix', reducing non-core activities and overhead costs, and a closer relationship with 'shareholders', suppliers and customers/clients). Evidence of activities and processes associated with transformational leadership are identified. Success of the New Zealand health reforms will be determined by the approach the new managers adopt to improve their organization's performance. Transformational leadership has been frequently linked to the successful implementation of significant organizational change in other settings (Kurz et al., 1988; Dunphy and Stace, 1990) but it is too early to assess whether this is applicable in a health care context.

Attitude of Health Personnel↗
PubMed1997

Immunocytochemical appearance of cytokines, prostaglandin E2 and lipocortin-1 in the CNS during the incubation period of murine scrapie correlates with progressive PrP accumulations.

The appearance of immunoreactive interleukin (IL)-1beta, IL-6 and tumour necrosis factor (TNF)-alpha, prostaglandin (PG) E2 and lipocortin-1 in the central nervous system was investigated during the development of lesions in a 301V/VM murine scrapie model. Focal PrP(Sc) deposition was present after 30 days of the 115-120 day incubation period; this immunoreactivity increased in intensity and distribution thereafter. Staining for IL-1beta and TNF alpha in perivascular macrophages, and PGE2 immunoreactivity in astrocytes, was detected in those areas showing PrP(Sc) deposition from 60 days. Increased GFAP and F4/80 immunoreactivity, indicating activation of astrocytes and microglia, was also evident in these areas from 60 days. Glial cytokine and lipocortin immunoreactivity was detected after 90 days, in the absence of clinical signs. The disease-induced cytokine, PG and lipocortin immunoreactivity occurred only in those brain areas showing PrP(Sc) deposition, glial activation and, in later stages, vacuolation. These findings support the concept that PrP(Sc) deposition induces glial cytokine production. These glial cytokines may contribute to the development of the pathological lesions in scrapie.

Animals↗
PubMed1997

PrP deposition, microglial activation, and neuronal apoptosis in murine scrapie.

The present study investigated the relationship among PrP deposition, microglial activation, vacuolation, and neuronal death in the hippocampus of the 301V/VM murine scrapie model (mean incubation period 117 +/- 1 days). PrP deposition was first detected after 30 days and microglial activation after 60 days. Vacuolation in the CA1 and CA2 pyramidal layer was present from 90 days onward. Only occasional in situ end labeling (ISEL)-positive neurons were present in the hippocampus of scrapie-infected mice from 75 days postinoculation (d.p.i.), except at 105 d.p.i. when relatively large numbers of apoptotic, ISEL-positive neurons in the CA1 hippocampal region were observed. Terminally ill animals showed almost complete loss of CA1 pyramidal neurons. Electron microscopy of the CA1 region at 105 days confirmed that these neurons were dying by apoptosis. These data suggest that microglial activation in scrapie is a response to abnormal PrP deposition rather than a response to neuronal cell loss.

Animals↗
PubMed1997

N-(5-substituted) thiophene-2-alkylsulfonamides as potent inhibitors of 5-lipoxygenase.

Compound 4k N-[5-(4-fluoro)phenoxythien-2-yl]methanesulfonamide is representative of a new class of potent inhibitors of 5-lipoxygenase (5-LO). These versatile compounds exhibit dose-dependent inhibition of 5-LO with IC50s ranging from 20-100 nM in the rat basophilic leukemia (RBL-1) cell homogenate assay and submicromolar IC50s in both the RBL-1 and human peripheral blood leukocyte (PBL) whole cell assays. Compound 4k also showed significant anti-inflammatory activity in the adjuvant arthritic rat at an oral dose of 3 mg/kg.

Administration, Oral↗
PubMed1997

Managing the gap: balancing advances in technology with advances in management practice.

Expenditure on information systems is widely anticipated to lead to improved management of health care resources. Despite large investments in hardware and software, these expectations are difficult to realise. Part of the difficulty lies in the manner in which information systems are applied to, rather than integrated within, organisations. This paper considers some of the the personal and organisational issues that need to be addressed to 'manage the gap' in balancing advances in information technology with advances in management practice. The issues identified are consistent with the concept of a learning organisation dealing with environmental change.

Case Management↗
PubMed1996

A novel ligand blot assay detects different hyaluronan-binding proteins in rat liver hepatocytes and sinusoidal endothelial cells.

We have developed a sensitive ligand blot assay to detect hyaluronan (HA) binding proteins in cell extracts using 125I-HA. Samples to be tested are electrophoresed using standard, nonreducing SDS-PAGE conditions, electro-transferred to nitrocellulose then blocked in buffer containing Tween 20. After incubation with 125I-HA the nitrocellulose is washed and HA-binding proteins are detected by autoradiography. This method was used to detect different HA-binding proteins in isolated rat liver cell preparations. Two HA-binding bands of 175 kD and 350 kD were detected in sinusoidal endothelial cells. Both bands were competed virtually 100% with nonlabeled HA. Using rat hepatocytes, the assay detected major bands at 85 kD and 180 kD. In addition, histones present in both cell types were readily detected in the low MW region. Thus, two different liver cell types show different HA-binding patterns. The blocking procedure is critical for successful renaturation of HA-binding activity, since substitution of BSA for Tween 20 did not result in detectable 125I-HA-binding. This ligand blot assay will be a powerful tool to detect HA-binding proteins in various other tissues and cell types.

Animals↗
PubMed1994

Tepoxalin, a novel immunosuppressive agent with a different mechanism of action from cyclosporin A.

Tepoxalin, a compound previously identified as a dual cyclooxygenase/lipoxygenase (CO/LO) inhibitor, is a potent inhibitor of T cell proliferation. Comparing the suppressive effects of tepoxalin and cyclosporin A (CsA) on OKT3-, PMA-, IL-2-, and PMA+ionomycin-induced T cell proliferations revealed marked differences in the mechanism of action between the two compounds. Whereas CsA was most effective in suppressing OKT3-stimulated proliferation, tepoxalin was more potent in inhibiting PMA-, PMA+ionomycin-, and IL-2-induced proliferation. Quantitative PCR (QPCR) assays used to detect cytokine messages showed that tepoxalin blocked IL-2 mRNA transcription in PMA- and PMA+ionomycin-, but not OKT3-stimulated T cells whereas CsA was most potent in inhibiting OKT3-induced IL-2 mRNA induction in these cells. Both tepoxalin and CsA did not inhibit the expression of IL-2R; however, only tepoxalin, but not CsA, inhibited the proliferation of IL-2-dependent blasts and the transcription of IFN-gamma, an IL-2-dependent target gene. Moreover, addition of exogenous IL-2 restored OKT3-induced proliferation to CsA- but not tepoxalin-treated cells. These data suggest that tepoxalin, but not CsA, suppressed T cell proliferation by inhibiting IL-2-induced signal transduction. Consistent with these findings, tepoxalin, unlike CsA, which was most potent when added at the initiation of OKT3 stimulation, was equally active, regardless of whether it was added at the beginning or 48 h after culture initiation. The difference in mechanism of action between tepoxalin and CsA was confirmed further by the synergistic suppressive effects on T cell proliferation upon co-administration of the two compounds.

Base Sequence↗
PubMed1994

A review of rural health restructuring in the New South Wales.

In 1993 the delivery of rural health services in New South Wales was restructured by the establishment of 23 district health services with the aims of diverting resources from administration to clinical services and enhancing decision-making at the local level. Implementation of the restructuring in its infancy was examined by structured interviews conducted with five general managers and 15 of their second-tier appointees. The organisational structure of the districts, the managerial attributes required of senior staff and approaches to change were emphasised. Political constraints on organisational decision-making such as organisational design were acknowledged and the importance accorded to demonstrable achievement in managing change and incorporating consultative techniques was recognised.

Decision Making, Organizational↗
PubMed1993

Intraosseous lipomas.

Intraosseous lipomas are considered to be rare tumours. We describe four cases and discuss their appearances and diagnosis. It is likely with the increasing frequency of computed tomography and magnetic resonance examinations of the lumbar spine that many more asymptomatic lesions will present to the radiologist and that these tumours are not as rare as the literature would suggest.

Adult↗
PubMed1990

Hyperostosis frontalis interna, acromegaly and hyperprolactinaemia.

The association between hyperostosis frontalis interna (HFI), acromegaly and hyperprolactinaemia was investigated. Thirty six acromegalic patients, of whom 19 had hyperprolactinaemia, were compared with 36 randomly-selected, age-sex matched controls. There was a higher prevalence of HFI in the skull X-rays of the acromegalic cohort (P = 0.0002) when compared to the control group. This difference was apparent in both men (P = 0.01) and women (P = 0.01). Acromegalic patients with hyperprolactinaemia also expressed HFI in a higher proportion of individuals than the control group (P = 0.0001). Intra- and interobserver variability was assessed and concordance with 100% and 97% in the moderate and severe HFI sub-groups. The following sub-group analysis was undertaken: acromegalics and those acromegalics with hyperprolactinaemia were compared with the controls and a highly significant distinction was confirmed (P = 0.0007 and P = 0.00001 respectively). A relationship between HFI severity and the patient's age was noted in both male and female acromegalics. Also, the severity of HFI appeared related to disease duration in female acromegalics. The cause of HFI remains unknown but appears to be strongly associated with acromegaly, particularly in the presence of co-existent hyperprolactinaemia. The association may have symptomatic significance and the presence of HFI should be confirmed or refuted in all patients with acromegaly.

Acromegaly↗
PubMed1990

Design, synthesis and bronchodilatory activity of a series of quinazoline-3-oxides.

A synthetic program of rational drug design was undertaken to develop a series of quinazoline-3-oxides as pulmonary-selective inhibitors of ovalbumin-induced, leukotriene-mediated bronchoconstriction. The most active and selective compounds contained a methyl group at the 4-position, a medium sized branched alkyl group at the 2-position, and a small electron donating group on the phenyl ring. Significant enhancement in selectivity was observed in comparing the pulmonary versus cardiovascular effects of these new bronchodilators with the effects of theophylline.

Animals↗