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Biomedical subjects

M Turner

Publications and source records attributed to M Turner.

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

Signal transduction through Vav-2 participates in humoral immune responses and B cell maturation.

B and T lymphocytes develop normally in mice lacking the guanine nucleotide exchange factor Vav-2. However, the immune responses to type II thymus-independent antigen as well as the primary response to thymus-dependent (TD) antigen are defective. Vav-2-deficient mice are also defective in their ability to switch immunoglobulin class, form germinal centers and generate secondary immune responses to TD antigens. Mice lacking both Vav-1 and Vav-2 contain reduced numbers of B lymphocytes and display a maturational block in the development of mature B cells. B cells from Vav-1(-/-)Vav-2(-/-) mice respond poorly to antigen receptor triggering, both in terms of proliferation and calcium release. These studies show the importance of Vav-2 in humoral immune responses and B cell maturation.

Animals↗
PubMed2001

The release of prion protein from platelets during storage of apheresis platelets.

BACKGROUND: Recent studies using a time-resolved fluoroimmunoassay method (dissociation-enhanced lanthanide fluoroimmunoassay) showed that platelets and plasma are the main reservoir of the normal isoform of cell-associated prion protein (PrPc) in human blood. The aims of the present study were to monitor PrPc levels in various fractions of apheresis platelets during storage by using the DELFIA method and to assess the association of this release with alpha-granule protein ss-thrombo-globulin and cytoplasmic LDH. STUDY DESIGN AND METHODS: Units of apheresis platelets (n = 6) were obtained from volunteer donors by the use of a cell separator and stored up to 10 days. Samples (7-9 mL) were aseptically collected from each unit on storage Days 1, 2, 3, 4, 5, 8, and 10. Platelet-poor plasma and apheresis platelets were prepared and the former split into two fractions, one centrifuged at 40,000 x g for 2 hours at 4 degrees C to remove microparticles. The spun microparticles, apheresis platelets and platelet samples, platelet-poor plasma, and high-spun plasma fractions were stored in a frozen state until they were tested. RESULTS: The results showed that the mean overall levels of PrPc throughout storage remained within 15 percent of Day 1 levels. In contrast, the mean cellular levels in platelets significantly decreased to 46 percent of Day 1 levels by Day 10 of storage (p<0.01), while the corresponding levels in plasma significantly rose as much as 329 percent (p<0.01). Moreover, although microparticle-bound PrPc was released during storage, it was increasingly superseded by soluble protein. PrPc and ss-thrombo-globulin release exhibited very similar patterns (p<0.01). In contrast, LDH showed a significant increase in high-spun plasma only toward the end of the storage period (p<0.01). CONCLUSION: These results indicate that PrPc is released from platelets during the storage of apheresis platelets and that this release is probably due mainly to platelet activation and alpha-granule release in the first few days of storage. Moreover, the released PrPc is increasingly composed of soluble proteins, as the storage period exceeds 5 days.

Blood Platelets↗
PubMed2001

Reduced anisotropy of action potential conduction in left ventricular hypertrophy.

INTRODUCTION: The aim of this study was to determine if anisotropic action potential conduction was altered during development of left ventricular hypertrophy (LVH). METHODS AND RESULTS: Isolated guinea pig left ventricular preparations from hearts that had developed LVH were used to measure conduction velocity in longitudinal and transverse orientations to the fiber direction. A variable degree of LVH was induced by placing a ring around the ascending aorta for 50 to 250 days. Results were compared with an age-matched control group that underwent a similar operation but with no ring placement. LVH was measured as the heart-to-body-weight ratio (HBR), which correlated with an increase of mean myocyte cross-sectional area. Longitudinal conduction velocity (LCV) declined progressively as HBR increased (mean +/- SD: sham vs LVH: HBR 3.74 +/- 0.30 g/kg vs 4.53 +/- 0.52 g/kg; LCV 72.8 +/- 15.5 vs 63.6 +/- 11.1 cm/sec). Mean transverse conduction velocity (TCV) was greater in LVH compared with control (20.5 +/- 4.7 cm/sec vs 25.4 +/- 8.1 cm/sec), but there was no significance in the trend as a function of HBR. The anisotropic ratio (LCV/TCV) significantly declined as HBR increased. The time constant of the foot of the action potential was smaller in the transverse compared with the longitudinal dimension. There was no influence of hypertrophy. CONCLUSION: The decrease of LCV and reduction of the anisotropic conduction ratio suggest remodeling of the tissue in LVH. The consequences for the generation of arrhythmias are discussed.

Action Potentials↗
PubMed2001

The role of the collectin system in pulmonary defence.

The human collectin system comprises the serum protein, mannose- binding lectin and the hydrophilic surfactant proteins A and D. The three proteins possess structural and functional similarities and are important components of innate immunity. Through a variety of mechanisms, including direct opsonisation and complement activation, they assist in host defence against a wide array of micro-organisms. Investigation of the roles of the surfactant proteins in pulmonary disease has been assisted recently by the development of transgenic knockout mice. Animals deficient in these proteins display susceptibility to certain bacterial and viral pathogens, stimulating research into the role of polymorphisms in these genes in human respiratory disease. The role of MBL in human pulmonary disease is less well established, although accumulating evidence suggests that it is a modifier for lung disease in tuberculosis and cystic fibrosis.

Adult↗
PubMed2001

Survival of Mycobacterium avium subsp paratuberculosis in amitraz cattle dip fluid.

OBJECTIVE: To determine the survival time of Mycobacterium avium subsp paratuberculosis in amitraz-based cattle dip fluid derived from an active dip site in northern New South Wales. PROCEDURE: Following inoculation of triplicate 5 L containers with faeces (0.5 g/L) from a clinical case of bovine paratuberculosis, samples collected up to 8 weeks after inoculation were examined by conventional and radiometric culture. M a paratuberculosis colonies were enumerated on solid media. RESULTS AND CONCLUSIONS: M a paratuberculosis survived in amitraz cattle dip fluid for up to 2 weeks, but not 3 weeks. Where 1% of solids in dip fluid is derived from a clinical case of paratuberculosis, dip fluid may contain viable M a paratuberculosis for at least 2 weeks. These findings have implications for the management of cattle dip sites.

Administration, Topical↗
PubMed2001

Rupture of the axillary (circumflex) nerve and artery in a champion jockey.

Rupture of the circumflex artery and nerve, without fracture or dislocation, is a rare traumatic event. Such a case is reported in a champion flat jockey who sustained blunt trauma to the shoulder after a fall during a race; the literature is also reviewed. At urgent surgical exploration, the axillary artery and nerve were repaired. The patient subsequently successfully returned to professional riding. This case highlights the difficulties in diagnosis and management.

Adult↗
PubMed2001

Neonatal electroencephalogram does not predict cognitive and academic achievement scores at early school age in survivors of neonatal extracorporeal membrane oxygenation.

Extracorporeal membrane oxygenation is an effective rescue treatment for severe cardiorespiratory failure in term or near-term neonates, although a wide range of neurologic sequelae have been noted in a substantial minority of survivors. The objective of the present study was to determine the value of the neonatal electroencephalogram (EEG) for predicting Wechler Preschool and Primary Scale of Intelligence-Revised (WPPSI-R), Wide Range Achievement Test, and Wide Range Assessment of Memory and Language scores at early school age in 66 testable survivors of extracorporeal membrane oxygenation who were not severely brain damaged. Technically satisfactory EEG recordings were obtained at least twice following admission to our nursery and prior to discharge. The EEGs were classified and graded according to standard criteria. The developmental test results of those who had only normal or mildly abnormal neonatal EEGs (group 1, n = 9) were compared with those who had at least one moderately or markedly abnormal recording (group 2, n = 57). School-age test and subtest scores were not statistically significantly worse in group 2 versus group 1 infants. No child in group 1 and five children in group 2 had WPPSI-R Full-Scale IQ scores of less than 70. Of the nine children in group 2 who had at least one markedly abnormal neonatal EEG recording (graded as burst suppression or as electrographic seizure), only two had abnormally low WPPSI-R Full-Scale IQ scores. We conclude that EEG recordings obtained during the neonatal course of neonates treated with extracorporeal membrane oxygenation do not predict cognitive and academic achievement test results in survivors at early school age who were testable and not severely brain damaged.

Brain Damage, Chronic↗
PubMed2001

Obtaining small parts with micromachining.

Microengineering techniques now deliver much smaller products with increased accuracy and cost-effectiveness. This article looks at the opportunities offered by today's micromachining methods.

Biomedical Engineering↗
PubMed2001

How to select a sterilisation process.

The decision on how to sterilise a medical device is dependant on many factors and as a result requires detailed investigation early in a project. The key factors are which processes are compatible with the materials and packaging used for the product. Other critical factors are cost, speed, the availability of a technology and level of customer support that is provided.

Decision Support Techniques↗
PubMed2000

Vav-2 controls NFAT-dependent transcription in B- but not T-lymphocytes.

We show here that Vav-2 is tyrosine phosphorylated following antigen receptor engagement in both B- and T-cells, but potentiates nuclear factor of activated T cells (NFAT)-dependent transcription only in B cells. Vav-2 function requires the N-terminus, as well as functional Dbl homology and SH2 domains. More over, the enhancement of NFAT-dependent transcription by Vav-2 can be inhibited by a number of dominant-negative GTPases. The ability of Vav-2 to potentiate NFAT-dependent transcription correlates with its ability to promote a sustained calcium flux. Thus, Vav-2 augments the calcium signal in B cells but not T cells, and a truncated form of Vav-2 can neither activate NFAT nor augment calcium signaling. The CD19 co-receptor physically interacts with Vav-2 and synergistically enhances Vav-2 phosphorylation induced by the B-cell receptor (BCR). In addition, we found that Vav-2 augments CD19-stimulated NFAT- dependent transcription, as well as transcription from the CD5 enhancer. These data suggest a role for Vav-2 in transducing BCR signals to the transcription factor NFAT and implicate Vav-2 in the integration of BCR and CD19 signaling.

Animals↗
PubMed2000

Development of T-leukaemias in CD45 tyrosine phosphatase-deficient mutant lck mice.

The CD45 tyrosine phosphatase lowers T-cell antigen receptor signalling thresholds by its positive actions on p56(lck) tyrosine kinase function. We now show that mice expressing active lck(F505) at non-oncogenic levels develop aggressive thymic lymphomas on a CD45(-/-) background. CD45 suppresses the tumorigenic potential of the kinase by dephosphorylation of the Tyr394 autophosphorylation site. In CD45(-/-) thymocytes the kinase is switched to a hyperactive oncogenic state, resulting in increased resistance to apoptosis. Transformation occurs in early CD4(-)CD8(-) thymocytes during the process of TCR-beta chain rearrangement by a recombinase-independent mechanism. Our findings represent the first example in which a tyrosine phosphatase in situ prevents the oncogenic actions of a SRC: family tyrosine kinase.

Animals↗
PubMed2000

Differential binding of mannose-binding lectin to respiratory pathogens in cystic fibrosis.

We have found that mannose-binding lectin binds to Burkholderia cepacia, an important pathogen in patients with cystic fibrosis, and leads to complement activation, but that this is not the case for Pseudomonas aeruginosa, the more common colonising organism in this disease. We suggest that patients with cystic fibrosis with mannose-binding-lectin deficiency will be at particular risk of B cepacia colonisation.

Burkholderia cepacia↗
PubMed2000

A new look at Syk in alpha beta and gamma delta T cell development using chimeric mice with a low competitive hematopoietic environment.

The Syk protein tyrosine kinase (PTK) is essential for B, but not T or NK, cell development, although certain T cell subsets (i.e., gamma delta T cells of intestine and skin) appear to be dependent on Syk. In this report, we have re-evaluated the role of Syk in T cell development in hematopoietic chimeras generated by using Syk-deficient fetal liver hematopoietic stem cells (FL-HSC). We found that Syk-/- FL-HSC were vastly inferior to wild-type FL-HSC in reconstituting T cell development in recombinant-activating gene 2 (RAG2)-deficient mice, identifying an unexpected and nonredundant role for Syk in this process. This novel function of Syk in T cell development was mapped to the CD44-CD25+ stage. According to previous reports, development of intestinal gamma delta T cells was arrested in Syk-/- -->RAG2-/- chimeras. In striking contrast, when hosts were the newly established alymphoid RAG2 x common cytokine receptor gamma-chain (RAG2/gamma c) mice, Syk-/- chimeras developed intestinal gamma delta T cells as well as other T cell subsets (including alpha beta T cells, NK1.1+ alpha beta T cells, and splenic and thymic gamma delta T cells). However, all Syk-deficient T cell subsets were reduced in number, reaching about 25-50% of controls. These results attest to the utility of chimeric mice generated in a low competitive hematopoietic environment to evaluate more accurately the impact of lethal mutations on lymphoid development. Furthermore, they suggest that Syk intervenes in early T cell development independently of ZAP-70, and demonstrate that Syk is not essential for the intestinal gamma delta T cell lineage to develop.

Animals↗