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Biomedical subjects

L Turner

Publications and source records attributed to L Turner.

At least 19 recordsLinked to original sources

Gene expression abnormalities in human glial tumors identified by gene array.

Novel genes specific for human oligodendroglioma and glioblastoma multiforme (GBM) were detected using the gene array analysis [18,376 genes Gene Discovery Array (GDA) from Incyte Genomics, Inc.]. Eleven genes were chosen based on the highest ratios of differential expression identified by GDA between histologically normal adjacent tissue and brain tumor tissue. The differential expression of those 11 genes was verified by semiquantitative RT-PCR and Northern analysis on 22 samples of glial and other tumors of the brain, as well as of normal embryonic and adult brain tissue. Gene no. 5 (an EST) was more expressed by GDA analysis in histologically normal adjacent brain tissue than in the corresponding oligodendroglioma. By RT-PCR, this gene was expressed in a number of brain tumors but not in normal adult and embryonic brain. By GDA analysis, gene no. 7 (oligophrenin-1) gave the highest ratio compared to other genes in brain tissue adjacent to the GBM vs. GBM. By RT-PCR, oligophrenin-1 was expressed in tumors and tumor-adjacent tissue, whereas meningioma and corpus callosum were negative. Gene no. 11 (an EST) was expressed only in brain tumors but not in normal brain by Northern analysis (message size 1.5 kb) and RT-PCR. GDA analysis successfully identified genes preferentially expressed in brain tumors, which was confirmed by Northern analysis and semiquantitative RT-PCR. The validity of gene arrays for tumor-specific gene discovery is discussed. Study of differential gene expression in glial tumors should help identify the mechanism/s of transformation of normal glial cells to malignant.

Brain Neoplasms↗

Effects of sleep loss on waking actigraphy.

STUDY OBJECTIVES: To assess the effect of sleep loss and the effect of a sedating drug on waking actigraphy DESIGN: N/A SETTING: N/A PARTICIPANTS: Seventeen healthy volunteers, aged 19-35 yrs INTERVENTIONS: Four night-day treatments presented in a Latin Square Design: placebo-8 hr time-in-bed (TIB), placebo-4 hr TIB, placebo-0 hr TIB, and diphenhydramine 50 mg-8 hr TIB. MEASUREMENTS AND RESULTS: After the appropriate TIB, medication was administered at 09:00 hr, the Multiple Sleep Latency Test at 09:30, 11:30, 13:30, 15:30, and 17:30 hr, and a 45 min performance battery at 10:30, 14:30, and 16:30 hr. Each day the volunteers wore actigraphs from 0700-1800 hrs. Decreasing TIB was associated with decreased daily mean sleep latency on the MSLT with 4 and 0 hrs differing from 8 hrs and each other. Daytime activity also was reduced by the reduced prior TIB. Increased inactivity relative to the 8 hr TIB developed between the 4 hr and 0 hr TIBs, with 4 hrs differing from 0 hrs, but not 8 hrs. Diphenhydramine 50 mg reduced mean daily sleep latency and increased percent inactive time relative to placebo. On the MSLT diphenhydramine was intermediate to 4 hr and 0 hr TIB and on actigraphy it was similar to 0 hr TIB. CONCLUSIONS: The difference in the effect of diphenhydramine on these actigraphy and MSLT may reflect the different sensitivities of the measures.

Adult↗

Conditions in grey seal pups (Halichoerus grypus) presented for rehabilitation.

A survey was carried out on the condition of 188 live grey seal (Halichoerus grypus) pups presented for rehabilitation from the coasts of south-west England between 1992 and 1998. The survey was carried out to assess the incidence of malnutrition, hyperthermia, respiratory and gastrointestinal conditions, and also the incidence of traumatic, skin, oral and ocular lesions. Malnutrition was a common finding in pups approaching weaning (mid-moult pups) and those at the point of weaning or postweaning (moulted pups) (62 per cent and 82 per cent, respectively). Separation from the dam, believed to be the main cause of malnutrition in grey seals, was encountered frequently in unweaned pups (91 per cent). Thirty-nine per cent of pups presented with a respiratory condition, 38 per cent with hyperthermia and 9 per cent with diarrhoea. Seven per cent and 14 per cent of pups had confirmed respiratory and gastrointestinal parasitic infestations respectively, although these were probably underestimates. Clinically significant traumatic lesions were seen in 41 per cent, oral ulceration in 26 per cent, ocular conditions in 13 per cent, nail bed infections in 13 per cent and oiling in 10 per cent of pups. Umbilical infections and other skin and oral conditions were also encountered. The incidence of these conditions is compared with data from dead grey seals, and clinical conditions in other pinniped species presented for rehabilitation.

Animals↗

Manifestation of random phase in a finite ensemble of a turbulent fluid

A field can be specified by a set of spectral coefficients, c(j)(t), relative to an expansion basis. In fluid turbulence, one often assumes the condition that if one were to extract data from an ensemble of realizations, one would find that the average, , would vanish unless i = i('), as in the case of a homogeneous ensemble in which the i's represent wave vectors. We analytically treat an extension to the case in which one has a larger number of coefficients than realizations, introducing intrinsic linear dependences that vitiate the stated condition.

Journal Article↗

Signature currents: a patch-clamp method for determining the selectivity of ion-channel blockers in isolated cardiac myocytes.

BACKGROUND: We describe a simple method using membrane potential ramps for rapidly determining the ion-channel selectivity of drugs that affect action-potential duration in isolated cardiac myocytes. The method allows the simultaneous assay of compounds on a number of ionic currents in a single cardiac cell. METHODS: Trains of membrane potential ramps were applied from -90 to +70 mV at 0.33 Hz to obtain a consistent "signature current," in which the major individual currents involved in the cardiac action potential could be easily identified. Confirmatory experiments were performed using known inhibitors of these currents. RESULTS: The identities of the currents in the signature were established by varying the concentrations of extracellular cations and by adding known ion channel blockers to superfusion solutions. Inhibition of each current had a characteristic and reproducible effect on the overall signature current. CONCLUSIONS: The consistent current signature in the presence and absence of blockers suggests that this method could be used for tertiary electrophysiological evaluation of compounds, eg, in a drug discovery program focusing on antiarrhythmic agents. The ability to assay for secondary effects of novel compounds against multiple currents in the target cell type is convenient and avoids the artefacts associated with using artificial expression systems.

Action Potentials↗

The antenatal ward care delivery map: a team model approach.

We begin by defining the concept of a 'CareMap', before briefly examining the context in which CareMaps emerged, as well as both their potential applications and the benefits arising from their implementation in health care services. We identify and discuss the history of, and critical aspects involved in, the development of the Antenatal Ward Care Delivery Map for the Mater Mothers' Hospital, Brisbane. We will address the multiple applications of, and specific benefits arising from, the formulation and implementation of the Antenatal Ward Care Delivery Map. Additionally, the relationship between the Care Delivery Map and other projects aimed at enhancing and maintaining high quality service delivery for patients across the continuum of care, will be explored. We examine the benefits of utilising the Care Delivery Map in professional education for clinical staff, as well as for health care consumers and their families. In conclusion, future projects enabled through the development of the Care Delivery Map are identified, as well as areas requiring further research.

Continuity of Patient Care↗

The rug3 locus of pea encodes plastidial phosphoglucomutase.

Two cDNA clones were isolated from pea (Pisum sativum L.) and their deduced amino acid sequences shown to have significant homology to phosphoglucomutases from eukaryotic and prokaryotic sources. The longer cDNA contained a putative transit-peptide-encoding sequence, supporting the hypothesis that the isolated clones represent the cytosolic and plastidial isoforms of phosphoglucomutase in pea. Plastid protein import assays confirmed that the putative plastidial isoform was targeted to the plastid stroma where it was proteolytically processed. Expression, co-segregation, linkage, and molecular analyses have confirmed that the rug3 locus of pea encodes plastidial phosphoglucomutase. Mutations at this locus result in a near-starchless phenotype of the plant.

Amino Acid Sequence↗

Real-time imaging of fluorescent flagellar filaments.

Bacteria swim by rotating flagellar filaments that are several micrometers long, but only about 20 nm in diameter. The filaments can exist in different polymorphic forms, having distinct values of curvature and twist. Rotation rates are on the order of 100 Hz. In the past, the motion of individual filaments has been visualized by dark-field or differential-interference-contrast microscopy, methods hampered by intense scattering from the cell body or shallow depth of field, respectively. We have found a simple procedure for fluorescently labeling cells and filaments that allows recording their motion in real time with an inexpensive video camera and an ordinary fluorescence microscope with mercury-arc or strobed laser illumination. We report our initial findings with cells of Escherichia coli. Tumbles (events that enable swimming cells to alter course) are remarkably varied. Not every filament on a cell needs to change its direction of rotation: different filaments can change directions at different times, and a tumble can result from the change in direction of only one. Polymorphic transformations tend to occur in the sequence normal, semicoiled, curly 1, with changes in the direction of movement of the cell body correlated with transformations to the semicoiled form.

Escherichia coli↗

Waldeyer's ring lymphoma presenting as massive oropharyngeal hemorrhage.

A case report of a patient presenting with massive oropharyngeal hemorrhage originating from lymphoma of the tonsil and it's management is discussed. Locally advanced or recurrent squamous cell carcinoma may manifest with massive oropharyngeal hemorrhage, however, it is unusual for Waldeyer's ring lymphoma to present in this fashion. Management of oropharyngeal malignancies presenting in this manner includes airway control, control of hemorrhage, and biopsy of the tumor. Hemorrhage control is provided by surgical exploration or intraarterial embolization. Extranodal lymphoma of the head and neck is not uncommon and is thoroughly discussed in the medical literature. Hemorrhage into the upper aerodigestive tract is occasionally observed in the patient with head and neck cancer. It usually occurs, however, in patients with squamous cell carcinoma that have been previously treated or in patients with locally advanced cancers. A comprehensive review of the literature has revealed no other reports of head and neck lymphoma presenting with massive oropharyngeal hemorrhage.

Aged↗

Addressing ethical issues in geriatrics and long-term care: ethics education at the Baycrest Centre for Geriatric Care.

An innovative program in ethics education exists at Baycrest Centre for Geriatric Care. This program can serve as a helpful model for long-term care and geriatric care facilities seeking to implement formal training programs in bioethics. Various aspects of the ethics education program are examined. In addition to describing the role of the ethics committee and research ethics board, consideration is given to case consultations, ethics rounds, the training of junior physicians and medical students, grand rounds and the planning of conferences and guest lectures. With regard to educational content in bioethics, health law, professional guidelines and the principlist approach of Beauchamp and Childress are used to explore the ethical dimensions of particular cases. Given the clinical context of the educational initiatives, the pedagogical approach is predominately case-based. While the bioethics literature emphasizes the patient-physician relationship, ethics education at Baycrest recognizes the importance of multiple professions. Physicians, nurses, social workers, speech pathologists, nutritionists and other health care providers are involved in ethical deliberation and education.

Aged↗

Hypoxia inhibits macrophage migration.

The chemokine monocyte chemoattractant protein (MCP)-1 plays a role in regulating the lymphocyte and macrophage infiltrate in ovarian cancer, but macrophages also accumulate in necrotic areas of the tumors where there is little MCP-1 expression (Negus, R. P. M. et al., Am. J. Pathol. 1997. 150: 1723-1734). Necrotic regions are likely to be hypoxic. In this study we show that hypoxia inhibits MCP-1-induced migration of THP-1 monocytic cells and human macrophages. In contrast, lymphocytes from peripheral blood migrate normally to an MCP-1 gradient in hypoxic conditions. The inhibition of monocyte migration by hypoxia is rapid and reversible. At the exposure times studied (30-90 min) hypoxia does not affect expression of the MCP-1 receptor CCR2B and cells exposed to hypoxia still respond to MCP-1 with an elevation of intracellular calcium. Although hypoxia is known to modulate gene expression, the inhibition of migration reported here was not due to the production of soluble factors, and mRNA expression of macrophage migration inhibitory factor was unchanged. Hypoxia-induced inhibition of chemotaxis was not limited to MCP-1. Hypoxia also inhibited the chemotactic response to macrophage inflammatory protein-1alpha, RANTES and the chemoattractant N-formyl-met-leu-phe, but hypoxic cells were still able to phagocytose opsonized red blood cells. We suggest that inhibition of migration by hypoxia is not due to gene regulation but is a reflection of metabolic changes in the cell. Transient hypoxia may regulate the distribution of macrophages in tumors and other inflammatory conditions.

Cell Hypoxia↗

Temperature dependence of switching of the bacterial flagellar motor by the protein CheY(13DK106YW).

The behavior of the bacterium Escherichia coli is controlled by switching of the flagellar rotary motor between the two rotational states, clockwise (CW) and counterclockwise (CCW). The molecular mechanism for switching remains unknown, but binding of the response regulator CheY-P to the motor component FliM enhances CW rotation. This effect is mimicked by the unphosphorylated double mutant CheY13DK106YW (CheY**). To learn more about switching, we measured the fraction of time that a motor spends in the CW state (the CW bias) at different concentrations of CheY** and at different temperatures. From the CW bias, we computed the standard free energy change of switching. In the absence of CheY, this free energy change is a linear function of temperature (. Biophys. J. 71:2227-2233). In the presence of CheY**, it is nonlinear. However, the data can be fit by models in which binding of each molecule of CheY** shifts the difference in free energy between CW and CCW states by a fixed amount. The shift increases linearly from approximately 0.3kT per molecule at 5 degrees C to approximately 0.9kT at 25 degrees C, where k is Boltzmann's constant and T is 289 Kelvin (= 16 degrees C). The entropy and enthalpy contributions to this shift are about -0. 031kT/ degrees C and 0.10kT, respectively.

Allosteric Regulation↗

Mice deficient in tumor necrosis factor-alpha are resistant to skin carcinogenesis.

Given the associations between chronic inflammation and epithelial cancer, we studied susceptibility to skin carcinogenesis in mice deficient for the pro-inflammatory cytokine TNF-alpha (refs. 5,6). TNF-alpha(-/-) mice were resistant to development of benign and malignant skin tumors, whether induced by initiation with DMBA and promotion with TPA or by repeated dosing with DMBA. TNF-alpha(-/-) mice developed 5-10% the number of tumors developed by wild-type mice during initiation/promotion and 25% of those in wild-type mice after repeated carcinogen treatment. TNF-alpha could influence tumor and stromal cells during tumor development. The early stages of TPA promotion are characterized by keratinocyte hyperproliferation and inflammation. These were diminished in TNF-alpha(-/-) mice. TNF-alpha was extensively induced in the epidermis, but not the dermis, in TPA-treated wild-type skin, indicating that dermal inflammation is controlled by keratinocyte TNF-alpha production. Deletion of a TNF-alpha inducible chemokine also conferred some resistance to skin tumor development. TNF-alpha has little influence on later stages of carcinogenesis, as tumors in wild-type and TNF-alpha(-/-) mice had similar rates of malignant progression. These data provide evidence that a pro-inflammatory cytokine is required for de novo carcinogenesis and that TNF-alpha is important to the early stages of tumor promotion. Strategies that neutralize TNF-alpha production may be useful in cancer treatment and prevention.

9,10-Dimethyl-1,2-benzanthracene↗

Building a better biotech company.

Invitrogen is a good case study for how to become successful in the rapidly changing field of biotechnology by observing basic business principles. It also shows that even the most successful companies make mistakes. The exciting opportunities that present themselves to high-technology companies in fast-growth fields can divert attention away from the most basic business tenets of quality, profitability, and market responsiveness. CEOs in the biotechnology sector would be well served to review their Business 101 lessons.

Biotechnology↗

Extrusion of testosterone pellets: a randomized controlled clinical study.

BACKGROUND: It has previously been shown that testosterone implantation is an effective and well accepted form of androgen replacement therapy, but that pellet extrusion was the most frequent side-effect. The present study aimed to reduce the extrusion rate. OBJECTIVE: To determine whether the washing of testosterone pellets to remove potentially surface-adherent particles decreased the rate of extrusion of pellet implants. DESIGN: Prospective, randomized parallel group design in a single centre with consecutive procedures to be randomized (1 : 1) into a wash or control group. PATIENTS: The study included 251 testosterone implantation procedures in men with known androgen deficiency. MEASUREMENTS: The primary endpoint, extrusion rate per procedure, was evaluated prospectively by telephone contact at 1 week and then 3 and 6 month intervals. Secondary end-points included peri-procedure adverse events (bleeding, skin reaction, excessive discomfort) noted at the time of implant. Bruising, bleeding and infection were also evaluated as later adverse events by telephone and personal follow-up. Explanatory variables recorded as possible covariables included the number of implants used, production batch number of the implants, the operator, as well as other demographic and medical factors. RESULTS: In the wash group, the extrusion rate was 12% per procedure (19 pellets from 15 subjects) whereas in the control group, the extrusion rate was 11.1% per procedure (18 pellets from 14 subjects), indicating no evidence of any benefit of the wash procedure (OR = 1. 09 [95% CI 0.47-2.6] per procedure). There was no evidence of benefit in secondary endpoints including total adverse events (7.1%, OR 1.28 [0.44-3.9], bleeding/bruising (8.8%, 1.23 [0.47-3.3]) and infection (4.0%, 1.54 [0.35-7.6]) per procedure. Among men reporting an infection requiring antibiotic treatment according to their own general practitioners, six/ten (60%) subsequently experienced an extrusion. There were no significant differences in extrusion rate between four different operators (P = 0.24) nor among 12 different batches of pellets used during the course of the study (P = 0.77). CONCLUSIONS: The pellet washing procedure used during implantation does not reduce the subsequent extrusion rate. The higher rate of both primary and secondary adverse events in this prospective study compared with the previous retrospective survey may reflect either more rigorous follow-up or a secular trend.

Drug Implants↗

George Rupert Palmer--DRG carrier and champion.

Prompted by the retirement of the distinguished health economist, researcher and academic, Professor George Rupert Palmer, the purpose of this paper is to reflect upon and acknowledge one of his many contributions to health services research and development. By employing a conceptual framework devised by Kimberly and de Pouvourville (1993) for analysis of the diffusion of innovations, this paper argues that Palmer played a crucial role in the diffusion into and within Australia of a particular casemix method, diagnosis related groups (DRGs). Textual and interview evidence presented in the paper supports the identification of George Rupert Palmer as the principal carrier of DRGs into Australia, and as one of its key champions within Australia.

Australia↗