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Biomedical subjects

M L Turner

Publications and source records attributed to M L Turner.

At least 55 records · Page 3Linked to original sources
PubMed1999

Distribution of cell-associated prion protein in normal adult blood determined by flow cytometry.

Leucocyte subpopulations from normally healthy individuals were identified by recognized combinations of fluorochrome-conjugated antibodies to CD markers and stained by different monoclonal antibodies (MAb) to normal cellular prion protein (PrPC), including the 3F4 MAb. Cell preparations were examined by three-colour flow cytometry. All mononuclear leucocyte subpopulations and platelets expressed PrPC, but polymorphonuclear leucocytes and red blood cells expressed little or no PrPC. The amounts of PrPC expressed by the different cells were calculated by comparison to bead standards. Mononuclear leucocytes expressed 3000-4000 molecules of antibody-reactive PrPC per cell. Resting platelets expressed around 1400 molecules of PrPC per cell, whereas activated platelets expressed around 4800 molecules of PrPC per cell. Extrapolation of these values to the amounts of the various cells in whole blood showed that platelet PrPC accounted for at least 96% of cell-expressed PrPC in blood. The PrPC on mononuclear cells and platelets was sensitive to enzymatic treatment of cells by proteinase k and phosphatidylinositol-specific phospholipase C. Certain anti-PrPC MAbs which showed equivalent intensity of staining to MAb 3F4 on fresh cells showed relative reductions of staining compared to MAb 3F4 on stored cells, indicating possible structural alterations of PrPC under these conditions.

Adult↗
PubMed1999

An international trial demonstrates suitability of a newly developed whole-blood ELISA kit for multicentre platelet HPA-1 phenotyping.

BACKGROUND: Neonatal alloimmune thrombocytopenia (NAIT) is in most cases due to pregnant women with HPA-1b platelet phenotype producing antibodies to HPA-1a platelets of the fetus, which may lead to intracranial haemorrhage with subsequent death or life-long morbidity. The availability of sensitive, reliable, straightforward, and inexpensive assays would enable large-scale screening in pregnancy and may help avoid NAIT. METHODS: A recently developed enzyme-linked immunosorbent assay (ELISA) was produced in kit form incorporating modified reagents and enabling distribution to 21 international Platelet Immunology and Blood Centres (see Acknowledgements). The kits were assessed using anticoagulated whole-blood samples stored up to 10 weeks at 4 degrees C. Each centre tested its own blood samples most of which had been previously typed by established assays. RESULTS: Of the 152 samples that were tested, all 31 HPA-1b phenotypes were correctly identified by the kit. The respective mean +/- standard deviation of the specific absorbances of HPA-1b and HPA-1a samples were: 0.52+/-0.15 and 0.12+/-0.06 (p<0.0005). In addition, the modified ELISA showed 100% concordance with PCR-SSP in the phenotyping of 93 donors. Finally, a comparison between freshly prepared and stored kits showed that the kit was stable for at least 2 years at 4 degrees C. CONCLUSIONS: The international trial showed that the modified whole-blood ELISA kit is very well suited for wide-scale screening in pregnancy. Moreover, the ELISA kit could be used for large-scale phenotyping of blood donors, with HPA-1b-typed individuals getting invited to become apheresis platelet donors for patients with NAIT.

Adult↗
PubMed1998

Open-label trial of oral nalmefene therapy for the pruritus of cholestasis.

The aims of this study were to determine whether long-term oral administration of the opiate antagonist nalmefene is associated with any beneficial effects in patients with pruritus secondary to cholestatic liver disease and to assess the safety of long-term administration of this drug to these patients. Fourteen patients with unrelieved chronic pruritus of cholestasis were studied. Scratching activity, independent of limb movements, was recorded continuously for 24-hour periods before and during treatment with an initial ameliorating dose of nalmefene. Simultaneously, during these periods, visual analogue scores (VASs) of pruritus were recorded every 4 hours while patients were awake. The dose of nalmefene, which initially was 2 mg orally twice daily, was increased during the study, usually until a satisfactory clinical response was achieved. Five patients experienced a transient opioid withdrawal-like reaction that did not preclude continuing with nalmefene therapy. Serum biochemical indices of cholestasis did not change appreciably during treatment. Thirteen patients reported amelioration of the perception of pruritus on nalmefene. In 5 patients, exacerbations of pruritus occurred approximately 4 weeks after an initial ameliorating dose had been reached; these exacerbations were managed by increasing the dose. Baseline mean values for VAS and scratching activity were higher than corresponding means during nalmefene therapy in 13 (P = .002) and 12 (P = .013) patients, respectively. Possible tolerance to nalmefene occurred in 3 patients. Three patients experienced marked exacerbation of pruritus after nalmefene therapy was suddenly discontinued. Blood levels of nalmefene were consistent with normal pharmacokinetics of the drug. These results suggest that nalmefene may have a favorable risk-to-benefit ratio when it is administered orally long-term to patients with the pruritus of cholestasis.

Administration, Oral↗
PubMed1998

New-variant Creutzfeldt-Jakob disease: the risk of transmission by blood transfusion.

New-variant Creutzfeldt-Jakob disease (nvCJD) was first described in the UK in 1996 and is thought to be related to the consumption of cattle suffering from bovine spongiform encephalopathy. Although only 29 cases have been confirmed to date, it is too early to predict the number of people who may currently be incubating the disease. Past experience suggests that sporadic CJD is rarely, if ever, spread by blood transfusion. However, it is unclear whether nvCJD may be transmissible by this route and if so, how easily. Assessing the potential risk of transmission of nvCJD by blood transfusion and evaluating the likely efficacy of proposed strategies to reduce this risk is, therefore, very difficult. This article summarizes the spectrum of transmissible spongiform encephalopathies in animals and man, the molecular and cellular biology of the prion protein and the continuing debate as to the nature of the infectious agent. The distribution of normal prion protein expression, the results of experimental transmission studies and the case reports and clinical studies on CJD transmission are reviewed. Finally, the extent of current knowledge and the potential utility of proposed strategies to reduce the risk of nvCJD transmission by blood transfusion are discussed.

Animals↗
PubMed1998

Comparative adhesion of human haemopoietic cell lines to extracellular matrix components, bone marrow stromal and endothelial cultures.

We used flow cytometry to characterize cell adhesion molecule expression of the human haemopoietic cell lines KG1a, K562, HL-60, NALM-6 and CEM. A 51chromium labelling assay was used to study the adhesion of these cell lines to extracellular matrix components and to bone marrow stromal and endothelial cultures. Both adhesion molecule expression and functional binding behaviour varied between cell lines. All five cell lines expressed the integrins alpha4beta1 and alpha5beta1 and all adhered to fibronectin. However, differences in intensity of expression of these integrins failed to correlate with extent of fibronectin adhesion. Inhibition experiments demonstrated that adhesion of KG1a to fibronectin was completely inhibited by divalent cation chelation and partially inhibited by RGDS peptides and chondroitinase ABC, suggesting that both alpha4beta1 and alpha5beta1 as well as CD44 were responsible for this interaction. Adhesion to bone marrow stromal and endothelial layers was superior to that to purified extracellular matrix components and was partially inhibited by divalent cation chelation. RGD peptides and anti-alpha4 monoclonal antibody also partially inhibited KG1a adhesion to bone marrow endothelium. Discordance between cell adhesion molecule expression and adhesive behaviour suggest that current phenotypic descriptions remain incomplete and reinforce the need for complementary functional binding studies.

Antigens, CD↗
PubMed1998

Developmental variation in stem-cell markers from human fetal liver and umbilical cord blood leukocytes.

Fetal tissues containing haematopoietic stem cells (HSC) are of potential value for allogeneic transplantation and gene therapy. Flow cytometry was used to investigate CD34+ cells from human fetal livers and umbilical cord (placental) blood (UCB). CD34+ cells, expressed as a proportion of CD45-positive leukocytes, were much more abundant in fetal livers (mean 38%) than in UCB (mean 0.3%), but fetal liver cells had lower proportions of CD34+HLA-DR+ and CD34+ CD38+ subsets. In fetal liver, there was a strong and highly significant inverse correlation between CD34+ cells (as a proportion of total leukocytes) and gestational age; no such relationship was found for subsets of CD34+ cells coexpressing CD38 or CDw90 (Thy-1), but CD34+HLA-DR+ cells were less abundant in first-compared to second-trimester livers. In UCB, a trend towards decreasing CD34+ cells (as a proportion of total leukocytes) with increasing gestational age in late pregnancy was also observed. The composition of fetal leukocytes changes during development, and therefore the timing of fetal HSC harvesting could be of relevance to transplantation outcome.

Antigens, CD↗
PubMed1998

Cutaneous tumors in patients with multiple endocrine neoplasia type 1 show allelic deletion of the MEN1 gene.

Multiple endocrine neoplasia type 1 (MEN1), the heritable tendency to develop tumors of the parathyroid, pituitary, and entero-pancreatic endocrine tissues, is the consequence of a germline mutation in the MEN1 gene. Endocrine tumors in these patients result when the mutant MEN1 allele is accompanied by loss of the normal MEN1 allele. Recently it was reported that MEN1 patients also exhibit several cutaneous tumors, including multiple angiofibromas, collagenomas, and lipomas. The purpose of this study was to examine skin lesions from patients with MEN1 for allelic loss of the MEN1 gene. Skin lesions from five patients with MEN1 were examined using fluorescence in situ hybridization. Six angiofibromas, three collagenomas, and one lipoma showed allelic deletion of the MEN1 gene. Allelic deletion was not observed in a melanocytic nevus or acrochordon from patients with MEN1. It was also not observed in an angiofibroma from a patient with tuberous sclerosis. These results suggest that loss of function of the wild-type MEN1 gene product plays a role in the development of angiofibromas, collagenomas, and lipomas in patients with MEN1.

Adolescent↗
PubMed1997

HIV-related eosinophilic folliculitis: a panel discussion.

Eosinophilic folliculitis is a common cause of morbidity in patients infected with the human immunodeficiency virus (HIV) and a marker of the acquired immunodeficiency syndrome (AIDS). No causative organism has yet been identified, although an aberrant Th2-type immune response to a follicular antigen appears relevant to pathogenesis. A variety of treatments have been reported to minimize the inflammatory component, relieve the concomitant pruritus, and/or favorably alter the cutaneous microenvironment.

AIDS-Related Opportunistic Infections↗
PubMed1996

Haemopoietic progenitor homing and mobilization.

Despite the widespread clinical exploitation of HPC mobilization and homing, the mechanisms central to these two phenomena are still unknown. However, the evolving concepts of multi-step adhesion cascades and demonstration of intracellular signalling which links lectin/carbohydrate binding with integrin activation in HPCs and other leucocytes suggests that HPC homing may be analogous to leucocyte homing in other systems. The complexity of this system is apparent from the data presented above, and more sensitive methods need to be developed to dissect the various adhesion pathways which may be involved.

Cell Adhesion↗
PubMed1996

The effect of music amplitude on the reaction to unexpected visual events.

The effects of music amplitude on participants' response time to randomly presented, unexpected, visual events were investigated. Ninety participants completed a motor-reaction task without music and with music played at 60, 70, or 80 dBA. Males preferred more intense music than females did, with males selecting a comfort level of 72 dBA and females, 66 dBA. However, participants' reaction time and the total time to respond to a randomly activated red light were independent of gender. All participants responded more quickly when the music was played at 70 dBA (close to their comfort level) than when it played at lower (60 dBA) or higher (80 dBA) amplitudes. It is proposed that people may react more quickly to visual events (e.g., the sudden appearance of a plane on the screen of an air traffic controller, or the unpredictable activation of a car's rear brake lights when driving) with music playing at a volume preset to maintain individual comfort levels against other situational background noise.

Adolescent↗
PubMed1995

Effects of naloxone infusions in patients with the pruritus of cholestasis. A double-blind, randomized, controlled trial.

OBJECTIVE: To determine whether endogenous opioids contribute to the pruritus of cholestasis by studying the effect of the opiate antagonist naloxone on the perception of pruritus and on scratching activity in patients with this form of pruritus. DESIGN: Double-blind, placebo-controlled, crossover trial with four periods. SETTING: Clinical research referral center. PATIENTS: 29 pruritic patients with liver diseases of various causes. INTERVENTION: Each patient received as many as two naloxone and two placebo solution infusions consecutively in random order. Each infusion lasted 24 hours. MEASUREMENTS: During the infusions, visual analog scores of pruritus were recorded every 4 hours while patients were awake; scratching activity independent of limb movements was recorded continuously. RESULTS: One patient had a mild reaction consistent with a naloxone-precipitated syndrome similar to opiate withdrawal. A significant 24-hour rhythm of scratching activity was seen in 7 of 11 patients for whom complete 96-hour data were collected. The mean of a visual analog score of the perception of pruritus (maximum, 10.0) recorded during naloxone infusions was 0.582 lower than that recorded during placebo infusions (95% CI, 0.176 to 0.988; P < 0.01). Furthermore, the ratio of the geometric mean hourly scratching activity during naloxone infusions to that during placebo infusions was 0.727 (CI, 0.612 to 0.842; P < 0.001) and was greater than 1.0 in only five patients. CONCLUSIONS: Naloxone administration is associated with amelioration of the perception of pruritus and reduction of scratching activity in cholestatic patients. Because of the opioid receptor specificity of the action of naloxone, these findings support the hypothesis that a mechanism underlying the pruritus of cholestasis is modulated by endogenous opioids and suggest that opiate antagonists may have a role in the management of this complication of cholestasis.

Adult↗
PubMed1995

Differential expression of cell adhesion molecules by human hematopoietic progenitor cells from bone marrow and mobilized adult peripheral blood.

The mechanisms responsible for mobilization of hematopoietic progenitor cells (HPC) from the bone marrow into the circulation are unknown. One possibility is that HPC downregulate cell adhesion molecule expression. We studied normal human bone marrow and adult peripheral blood following 4 g/m2 cyclophosphamide and recombinant human granulocyte colony-stimulating factor (rHuG-CSF). Each sample was studied for the coexpression of CD34 and a panel of cell adhesion molecules by dual immunocytometry. Bone marrow HPC express the immunoglobulin gene superfamily members of ICAM-1 (CD54), PECAM-1 (CD31) and LFA-3 (CD58), the integrins VLA-4 (CD49d/CD29), VLA-5 (CD49e/CD29) and LFA-1 (CD11a/CD18), L-Selectin (CD62L), HCAM (CD44) and CD36. Mobilized peripheral blood HPC display less expression of LFA-3 (CD54) and VLA-5 (CD49e). Significant differences in cell adhesion molecule expression do exist between sessile and circulating HPC, but the biological relevance of these observations is currently unclear.

Adult↗