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Biomedical subjects

D Turner

Publications and source records attributed to D Turner.

At least 91 records · Page 5Linked to original sources

Identification of inducible nitric oxide synthase in human macrophages surrounding loosened hip prostheses.

Exposure of rodent macrophages to certain cytokines and endotoxin results in the synthesis of inducible nitric oxide synthase (iNOS or NOS-II) leading to the production of large amounts of nitric oxide (NO). Cultures of human macrophages, in contrast, do not produce iNOS after cytokine stimulation, and their ability to act as a physiological source of NO remains questionable. Here we have used immunohistochemistry and in situ hybridization to demonstrate the presence of iNOS within human macrophages present in the interfacial membrane and pseudocapsule that surround failed prosthetic hip joints. Synovial tissue recovered from normal human joints did not express iNOS. Many of the iNOS-positive macrophages within the interfacial membrane had phagocytosed large amounts of polyethylene wear debris, suggesting a role for phagocytic stimuli in inducing iNOS in human macrophages. These findings additionally support a role for NO in modulating the localized bone resorption that accompanies the aseptic loosening of prosthetic joints.

Aged↗

Primary biliary cirrhosis associated with antiphospholipid syndrome.

A 47-year-old female was admitted for severe pain of 1 month's duration in the third and fourth toes of the right foot, culminating in gangrene. Laboratory findings revealed liver enzyme abnormalities, and anti-mitochondrial, anti-phospholipid and antinuclear and doubtful anti-DNA antibodies. Systemic lupus erythematosus (SLE) was excluded on clinical grounds after a 6-year follow-up. Therefore, a diagnosis was made of the primary antiphospholipid syndrome, complicated by microvasculopathy, and associated with primary biliary cirrhosis.

Antiphospholipid Syndrome↗

Genetic variation in the interleukin 10 gene promoter and systemic lupus erythematosus.

OBJECTIVE: To investigate interleukin 10 (IL-10) gene promoter polymorphisms in systemic lupus erythematosus (SLE) and its clinical subsets. METHODS: DNA from 76 Caucasian patients with SLE and 119 controls as genotyped for 3 defined dimorphic polymorphisms (G or A at position -1082, C or T at position -819, C or A at position -592) in the promoter region of the IL-10 gene, using the polymerase chain reaction to amplify the IL-10 gene promoter and oligonucleotide probes specific for each allelic sequence. The frequency of genotypes was compared between patients with SLE and controls, and between clinical subsets of patients with the disease. RESULTS: There was no significant change in the allele frequency of the three IL-10 gene promoter dimorphic polymorphisms in the SLE group compared with controls. However, when subgrouped according to autoantibody status and clinical features, IL-10 -1082*G, -819*C, and -592*C alleles were increased in patients possessing Ro autoantibodies and those with renal involvement. These alleles are in preferential allelic association, namely GCC, ACC, and ATA haplotypes, and the GCC haplotype was increased in these patient subgroups. CONCLUSION: Polymorphisms within the IL-10 gene promoter that are associated with high IL-10 levels may be important in the development of certain clinical features in SLE.

Adolescent↗

Kinesin movement on glutaraldehyde-fixed microtubules.

Glutaraldehyde-cross-linked microtubules were investigated as substrates for kinesin motility. Microtubules, formed in vitro from chicken brain tubulin, were stabilized with Taxol and chemically fixed with glutaraldehyde. The degree of tubulin monomer cross-linking as a function of time and glutaraldehyde concentration was characterized using polyacrylamide gel electrophoresis. Atomic force microscopy of fixed microtubules indicated that the cross-linking is sufficient to stabilize the gross structure of the microtubules against air drying or a distilled water challenge. Kinesin movement on immobilized, fixed microtubules was determined using a kinesin-coated bead motility assay observed with differential interference contrast microscopy. Within measurement error, kinesin bead movement velocities were independent of the degree of microtubule cross-linking. Binding affinity, however, decreased with increased cross-linking. Although air- and water-challenged microtubules did not support kinesin motility, a dilute suspension of glutaraldehyde-fixed microtubules in buffer supported kinesin motility for at least 2 days without any substantial degradation of activity. Fixed microtubules may be useful for several applications, including affinity purification of microtubule-associated proteins and motility measurements under extreme conditions of temperature and other variables.

Animals↗

Conformal radiation therapy with fixed shaped coplanar or noncoplanar radiation beam bouquets: a possible alternative to radiosurgery.

PURPOSE: Three-dimensional (3D) geometric conformation of the therapeutic dose volume to the shape of a target tissue volume is the motivation for both conformal radiotherapy and radiosurgery. Although noncoplanar arcs have a clear physical and geometric advantage over fixed fields for small spherical targets, those advantages are reduced for large or irregularly shaped targets where static fields can be individually shaped. We have developed a system that allows efficient and flexible design and reliable delivery of customized "bouquets" of fixed nonopposed coplanar or noncoplanar shaped fields, resulting in highly uniform dose distributions. This report describes our initial experience using beam bouquets to treat intracranial lesions. METHODS AND MATERIALS: Patients with primary (11) or metastatic (4) intracranial lesions with a maximum diameter less than approximately 6 cm, most of whom candidates for single-fraction radiosurgery, were treated with beam bouquets of four to eight nonopposed coplanar or noncoplanar beams. Doses ranged from 16-20 Gy in four fractions for recurrent lesions (8) to 45 to 68 Gy in 25 to 34 fractions for primary lesions (7). The patients were immobilized with custom foam head supports and face masks attached to a fixed base plate. Planning computed tomography scans were acquired, from which the physician developed the custom beam bouquet using 3D treatment-planning tools. The bouquet was designed based primarily on geometric concerns. The bouquet was subsequently modified to add wedge filters chosen by vector analysis of dose gradients to achieve uniform dose over the volume of beam crossfire. At the time of treatment, the isocenter was placed using the instructions provided by the treatment-planning system and pretreatment orthogonal port films were compared to digitally reconstructed radiographs (DRR) to assure proper isocenter placement. For several situations, the 3D dose distributions resulting from alternative coplanar and noncoplanar plans were compared. RESULTS: Each patient was treated without incident. Daily pretreatment port films showed excellent reproducibility of isocenter placement in 87% of setups. With short follow-up (0-12 months), two patients with recurrent glioblastoma experienced clinical deterioration 2 to 4 weeks following treatment. One had increased edema on scans and responded to steroids. Six patients clinically improved following radiation therapy. Review of alternative treatment plans reveals that the relative utility of coplanar vs. noncoplanar beams is likely dependent on the location of the lesion. Noncoplanar beam bouquets are likely preferable to coplanar beams when the target is located in the central regions of the head. Coplanar beams are likely adequate, and possibly preferable, for peripherally located targets. CONCLUSION: The biological advantages of fractionation and the physical advantages of radiosurgery are exploited with this approach. The use of multiple nonopposed coplanar or noncoplanar conformal wedged fields provides a uniform dose to the target and acceptable dose gradient at the target edge. This technique may prove to be an alternative to arc-based radiosurgery in some settings and has the potential advantages that fractionation should improve the therapeutic ratio, and each beam can be individually shaped to conform to irregularly shaped targets. Additional studies are underway to improve this system and better define its utility.

Adult↗

Digital data capture for electronic patient record systems.

The importance of digital data capture in optimizing the benefit and cost savings provided by an EPRS has been shown. Data will come from several sources including ADT systems, laboratory computer systems, and transcription computers, and the data will need to be stored in the electronic patient record. The HL7 standard provides a common language for new systems to exchange data. For older systems, an interface engine or toolkit may be necessary to transfer the data from another hospital system to the EPRS. In any case, capturing and storing digital data will greatly enhance the usability of an EPRS.

Computer Communication Networks↗

Effect of surface plasma treatment on the chemical, physical, morphological, and mechanical properties of totally absorbable bone internal fixation devices.

The purpose of this work was threefold: to enhance the adhesion between the reinforced absorbable calcium phosphate (CaP) fibers and the absorbable polyglycolide acid (PGA) matrix, to improve the hydrolytic degradation of the CaP fibers, and preliminarily to evaluate the cytotoxicity of the plasma treated surface of CaP fibers. A CH4 plasma treatment was used to achieve these goals. The microbond method was used to evaluate the effects of the plasma treatment on the interfacial shear strength between the PGA matrix and CaP fibers. The treatment increased the mean interfacial shear strength of the CaP/PGA composite system by 30%. AFM data showed that CH4-treated CaP fibers had considerable microscopic surface roughness, which facilitated mechanical interlocking between the reinforced CaP fibers and PGA matrix. The untreated and plasma-treated fibers were also subjected to in vitro hydrolytic degradation in a phosphate buffer solution of pH 7.44 at 37 degrees C for up to 15 h. CH4 plasma treatment resulted in a considerable lower polar term of the surface energy and a significantly higher disperse term in water media. This change in the proportion of surface energy terms may reduce the capillary wicking phenomena of water through the CaP fiber/PGA matrix interface. The CaP fiber dissolution studies revealed that both CH4 and Parylene plasma polymer coatings appeared to reduce the solubility of CaP fibers, and that the magnitude of reduction was higher in an acidic than a physiologic pH environment. A preliminary cytotoxicity test revealed that both CH4 and Parylene plasma-treated CaP fibers were noncytotoxic. Additional research should be done to determine the optimum plasma conditions and the possible use of other plasma gases to improve the interfacial shear stress of the composite and the dissolution properties of CaP fibers.

1-Propanol↗

Thrombin-induced increase of F-actin in human umbilical vein endothelial cells.

The actin cytoskeleton of the endothelium plays a key role in the maintenance of an endothelial permeability barrier. Inflammatory agonists, such as thrombin, cause an increase in vascular permeability associated with changes in the actin filament system. However, the full nature and extent of agonist-induced changes to endothelial actin have not been documented. We have studied the actin cytoskeleton in human umbilical vein endothelial cells (HUVEC) growing on tissue culture plastic coverslips or 0.4-micron pore-size polycarbonate membranes. We found: (1) Thrombin (0.3 U/ml) induced a rapid (within 5 min) increase in the number of microfilaments in HUVEC. (2) Using a quantitative assay for cellular filamentous actin (F-actin), thrombin induced a 1.7-fold increase in HUVEC F-actin within 1 min which persisted for at least 30 min. (3) Blockage of the thrombin-induced intracellular calcium ion ([Ca2+)i) signal did not block the thrombin-induced increase in F-actin, and calcium ionophores did not cause an increase in F-actin. (4) Protein kinase C inhibitors (calphostin C and staurosporine both at 100 nM) partially blocked the actin increase. Higher doses of staurosporine (500 nM) resulted in complete blockage of the thrombin-induced increase in F-actin. (5) Treatment with phorbol ester (100 nM PMA) or mezerein (100 nM) did not produce significant changes in F-actin content. These results suggest that an increase in [Ca2+]i is not necessary for the thrombin-induced increase in endothelial F-actin and, further, that the effect is mediated by protein kinases not yet identified.

Actins↗

Alterations in reverse cholesterol transport associated with programmable implantable intraperitoneal insulin delivery.

Our previous studies have suggested that intraperitoneal (IP) insulin delivery may be associated with alterations of reverse cholesterol transport (RCT). We thus studied two parameters of RCT. We performed RCT studies in 10 C-peptide-negative type I diabetic patients who were randomized into two groups. The experimental (A) and control (B) groups were studied at -3 and 0 months before and +3 and +6 months after IP pump subcutaneous (SC) insulin use. The first step in RCT was estimated by measuring patient serum-mediated 3H-cholesterol efflux from cultured fibroblasts. Cholesteryl ester transport protein (CETP) activity was assessed by a solid-phase assay. No changes in glucose control occurred during the study. Total low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol, apoprotein B, and apoprotein A-I remained unchanged during the study. Cholesterol efflux from group A increased from baseline after 3 months of IP insulin by 9.5% +/- 3.4% (mean +/- SE, P < .05), whereas in group B patients it decreased negligibly by 1.5% +/- 2.9% (P = .045 for changes between groups). CETP activity increased from baseline by 25.3% +/- 7.7% (P < .05) in group A after 3 months of IP insulin, whereas in group B it changed little, -1.5% +/- 7.9%, with modest differences between groups (P = .16). These data indicate that (1) serum from patients treated long-term with IP insulin delivery may enhance cholesterol efflux from fibroblasts and CETP activity, and (2) these effects appear independent from glucose control, implying a direct effect by IP insulin.

Adult↗

Transmission of pressure across the chest wall during the rapid thoracic compression technique in infants.

During the rapid thoracic compression maneuver in infants, the transmission of pressure from compression jacket to pleural space and airway is less at functional residual capacity than at end inspiration. To examine whether reduced pressure transmission at functional residual capacity vs. higher lung volumes is explained by passive characteristics of the chest wall rather than by respiratory muscle activity, we assessed the pressure transmitted across the chest wall in nine anesthetized infants and young children after muscle relaxation. We measured esophageal and airway occlusion pressure during chest compressions at different lung volumes determined by varying distending pressure. In six subjects studied under static conditions, there was an approximately linear relationship between distending pressure and the proportion of pressure transmitted to the airway and esophagus from the compression jacket. The mean r2 value (95% confidence interval) was 0.80 (0.09) for pressure transmission to the airway and 0.85 (0.04) for pressure transmission to the esophagus. This relationship between lung volume and pressure transmission observed under static conditions was also demonstrated dynamically. Thus the reduced transmission of pressure from compression jacket to airway and pleural space at low lung volumes occurs independently of respiratory muscle activity.

Anesthesia↗

Stacked inspiratory spirometry reduces pulmonary shunt in patients after coronary artery bypass.

Atelectasis is a major factor in postoperative morbidity for patients undergoing cardiopulmonary surgery. We evaluated the effectiveness of stacked inspiratory spirometry (STIS) in 17 patients status postcoronary artery bypass graft in a nonrandomized fashion. We measured pulmonary shunt as an endpoint, and compared the magnitudes before and after the STIS maneuver. Our results showed an 8.66 percent reduction in pulmonary shunt (p < 0.05). The reduction in shunt was modest; however, repetitive maneuvers might result in greater improvement.

Aged↗

Nonsteroidal anti-inflammatory drugs for the prevention of colon cancer.

OBJECTIVE: To summarize the results of animal and human studies of the effect of nonsteroidal anti-inflammatory drugs (NSAIDs) on neoplastic growth in the colon and to outline the possible mechanisms involved. DATA SOURCES: Research articles published in English before June 1992 were identified from MEDLINE. STUDY SELECTION: Nine articles on the polyp-cancer sequence were reviewed, 8 on the apparent pathophysiologic aspects of tumour inhibition by NSAIDs and 22 on animal and human research into the effect of NSAIDs on colon carcinogenesis. RESULTS: The results of animal and human research into the anticarcinogenic effect of NSAIDs suggest that the drugs are effective in preventing tumour growth in the colon. CONCLUSIONS: Intervention studies in humans are necessary to elucidate the therapeutic possibilities of NSAIDs, particularly in populations at increased risk for the development of colon cancer.

Animals↗

Classification of mutations at the HLA-A locus by use of the polymerase chain reaction.

We investigated whether the polymerase chain reaction (PCR) could be used to determine the mechanism of mutation in lymphocyte clones mutated at the HLA-A locus. Three polymorphisms, at Factor XIIIA, D6S109, and intron 3 of the HLA-A gene, were used to study a series of clones previously characterised by Southern blotting (SB) at multiple loci on chromosome 6. For detection of loss of heterozygosity, the results of PCR and SB were concordant in 140 of 141 clones when polymorphism in the Factor XIIIA region was studied and in 144 of 145 clones when polymorphism in the HLA-A gene was studied. For classification of the mechanism of mutation, PCR and SB gave the same result in 88 of 92 clones (96%) when a combination of the HLA-A and Factor XIIIA polymorphisms was used and in 46 of 47 clones (98%) when a combination of the HLA-A and D6S109 polymorphisms was used. The results indicate that PCR provides a simple and reliable method for categorising mutations at the HLA-A locus as arising from mitotic recombination, deletion, or from presumptive minor changes within the gene. Rare events such as gene conversion, nondisjunction, or large deletions extending to the telomere will be misclassified. However, such events are rare for mutations at this locus.

Base Sequence↗