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Biomedical subjects

R A Jones

Publications and source records attributed to R A Jones.

At least 73 records · Page 4Linked to original sources
PubMed1997

Circulating plasma cells in multiple myeloma: characterization and correlation with disease stage.

The aim of this study was to develop a flow cytometric test to quantitate low levels of circulating myeloma plasma cells, and to determine the relationship of these cells with disease stage. Cells were characterized using five-parameter flow cytometric analysis with a panel of antibodies, and results were evaluated by comparison with fluorescent consensus-primer IgH-PCR. Bone marrow myeloma plasma cells, defined by high CD38 and Syndecan-1 expression, did not express CD10, 23, 30, 34 or 45RO, and demonstrated weak expression of CD37 and CD45. 65% of patients had CD19- 56+ plasma cells, 30% CD19- 56(low), and 5% CD19+ 56+, and these two antigens discriminated myeloma from normal plasma cells, which were all CD19+ 56(low). Peripheral blood myeloma plasma cells had the same composite phenotype, but expressed significantly lower levels of CD56 and Syndecan-1, and were detected in 75% (38/51) of patients at presentation, 92% (11/12) of patients in relapse, and 40% (4/10) of stem cell harvests. Circulating plasma cells were not detectable in patients in CR (n = 9) or normals (n = 10), at a sensitivity of up to 1 in 10,000 cells. There was good correlation between the flow cytometric test and IgH-PCR results: myeloma plasma cells were detectable by flow cytometry in all PCR positive samples, and samples with no detectable myeloma plasma cells were PCR negative. Absolute numbers decreased in patients responding to treatment, remained elevated in patients with refractory disease, and increased in patients undergoing relapse. We conclude that flow cytometry can provide an effective aternative to IgH-PCR that will allow quantitative assessment of low levels of residual disease.

Adult↗
PubMed1997

Outcome of subarachnoid haemorrhage. An analysis of surgical variables, cognitive and emotional sequelae related to SPECT scanning.

A group of 48 patients, consecutive apart from exclusions, from a 1-year series of 60 cases of aneurysmal subarachnoid haemorrhage (SAH), was reviewed, in respect of clinical and radiological features, surgical management, clinical outcome, psychological distress and psychometric status, the neuropsychological assessment being compared with a closely-matched group of controls, the postoperative assessment being accompanied by a single positron emission computed tomogram (SPECT) scan. A review of those features which might have been expected to have a bearing on cognitive outcome (CT abnormalities at the outset, angiographic vasospasm, operative aneurysmal leakage, temporary vessel occlusion) failed to show a significant difference on cognitive tests. There was, however, a cognitive deficit shown by the patient group as a whole, when compared with the controls. Thus, SAH itself, the initial insult, would appear to be the essential factor in the production of persistent cognitive deficits.

Activities of Daily Living↗
PubMed1997

Multidisciplinary collaboration: conceptual development as a foundation for patient-focused care.

A participatory action research design using a combination of qualitative methods was used to induce a conceptual definition of multidisciplinary collaboration and to develop a measure of the concept among health care workers. Conclusions from the study include strategies to foster multidisciplinary collaboration among health care workers when health care delivery systems are being reengineered.

Cooperative Behavior↗
PubMed1997

Program evaluation of a unit reengineered for patient-focused care.

A quasi-experimental research design was used to determine how successful a work redesign project based on the philosophy of patient-focused care was in meeting the established goals of increased multidisciplinary collaboration, improved satisfaction for health care clients and providers, decreased cost of care, and decreased length of stay. Results indicate that multidisciplinary collaboration decreased for all health care providers, especially the health care employee group that underwent a major role revision. Patient and health care provider satisfaction increased. The cost of care was budget neutral as a result of the shift of employee costs from centralized departments to units. Length of stay decreased.

Adolescent↗
PubMed1997

Probing interactions between viral DNA and human immunodeficiency virus type 1 integrase using dinucleotides.

Retroviral integrases are essential for viral replication and represent an attractive chemotherapeutic target. In the current study, we demonstrated the activity of micromolar concentrations of dinucleotides against human immunodeficiency virus type 1 (HIV-1), HIV type 2 (HIV-2), simian immunodeficiency virus, and feline immunodeficiency virus integrases. The structure-activity relationship indicates that 5'-phosphorylation enhances potency and that phosphodiester and sugar modifications affect the inhibition of HIV-1 integrase. Base sequence selectivity was observed: pAC, pAT, and pCT were the most potent inhibitors, whereas pAA, pGA, and pGC showed low activity at 100 microM. The inhibition by pAC is consistent with the interaction of the enzyme with the 5' end of the noncleaved strand (5'-AC-3'). The linear and cyclic dinucleotides released by the 3'-processing reaction did not affect enzymatic activity at physiological concentrations. An increase in the length to trinucleotides or tetranucleotides enhanced potency by only 2-3-fold, suggesting that two neighboring bases may be sufficient for significant interactions. Inhibition of a truncated (50-212) integrase mutant and global inhibition of all nucleophiles in the 3'-processing reaction suggest that dinucleotides bind in the catalytic core. All of the active dinucleotides inhibited enzyme/DNA binding in their respective IC50 range. Although the dinucleotides tested showed no antiviral activity, these observations demonstrate the usefulness of dinucleotides in elucidating enzyme mechanisms and as potential ligands for cocrystallization and as lead structures for development of antivirals.

Animals↗
PubMed1997

Pulmonary embolism: detection with MR perfusion imaging of lung--a feasibility study.

PURPOSE: To evaluate the feasibility of magnetic resonance (MR) perfusion imaging in the human lung to help detect perfusion defects distal to suspected pulmonary embolism. MATERIALS AND METHODS: Seven patients suspected of having pulmonary embolism first underwent ventilation-perfusion lung scintigraphy followed by MR perfusion imaging with rapid acquisition of two sets of dynamic images in the coronal and transaxial planes. A bolus of 0.05 mmol per kilogram of body weight gadopentetate dimeglumine or gadodiamide was administered. Single images obtained in each section that showed peak signal intensity from the first passage of contrast material were evaluated visually. An analysis of change in signal intensity over time was performed both on a pixel-by-pixel basis and in selected regions of interest. RESULTS: In the seven patients, a total of 18 regions of lung tissue with perfusion defects were shown on the ventilation-perfusion scans. In 16 of these regions, MR perfusion images showed a reduced peak signal intensity during first passage of the contrast agent. Perfusion defects could be detected in both the coronal and the transaxial planes on MR perfusion images. CONCLUSION: MR perfusion imaging was feasible for detection of perfusion defects distal to a pulmonary embolism.

Adult↗
PubMed1997

Reduced expression of tissue transglutaminase in a human endothelial cell line leads to changes in cell spreading, cell adhesion and reduced polymerisation of fibronectin.

Tissue transglutaminase (tTgase, type II) is a Ca2+-dependent GTP binding protein which crosslinks proteins via (epsilon)((gamma)-glutamyl)lysine bridges. Although essentially a cytosolic enzyme there is increasing evidence to suggest the enzyme is externalised where it may play a role in extracellular matrix organisation. To investigate the function of this enzyme in a human umbilical endothelial cell line ECV304 tTgase expression was reduced in these cells by up to 90% by stable transfection with a 1.1. kb antisense construct in the plasmid vector pSG5. Two clones showing a reduction in expression of tTgase activity of 70 and 90% have been isolated and characterised. These clones show a number of phenotypic differences when compared to the parent cell line and the transfected controls which include reduced cell spreading and a decreased adhesion of cells on different substrata as measured by their susceptibility to removal by trypsin. Reduced cell spreading in the antisense transfected clones was accompanied by a decrease in the crosslinking of fibronectin into polymeric multimers which could be correlated to the amount of tTgase externalised by cells. A novel assay was developed to measure externalised tTgase activity which is cell mediated, inhibited by preincubation of cells with anti-tTgase antibody and relies on the incorporation of biotinylated cadaverine into fibronectin. The results of these experiments suggest that externalised tTgase may play a key role in a number of cell behavioural patterns which might be related to the enzymes ability to bind and crosslink fibronectin.

Antibodies, Monoclonal↗
PubMed1996

Characterization of IGFBP-3, PAI-1 and SPARC mRNA expression in senescent fibroblasts.

The RNA species encoded by IGFBP-3 (insulin-like growth factor binding protein-3), PAI-1 (plasminogen activator inhibitor-1) and SPARC (secreted protein-acidic and rich in cysteine; a.k.a. osteonectin) are overexpressed in senescent human diploid fibroblasts (HDF). Their extracellular products have the ability to modulate cell growth in culture and have been shown to have inhibitory effects on DNA synthesis and/or cell growth. This overproduction may contribute to a number of features of aging, including osteoporosis, atherosclerosis and diabetes mellitus type II. Based on analysis of steady-state mRNA levels, which showed similar patterns for all three along with overexpression in senescent cells, we further investigated their transcription rates and stability to determine reasons for their overexpression and to determine if coordinate gene regulation was involved. Characterization of the rates of transcription and the levels of message stability of these genes in early passage (young) versus late passage (old) HDF revealed that IGFBP-3, PAI-1 and SPARC are coordinately overexpressed but not regulated by a unique or simple mechanism encompassing all three transcripts. Only PAI-1 shows an increase in the rate of transcription, while all three show evidence that their overexpression is due to an increase in the stability of RNA. Thus, the overexpression of these genes in senescent fibroblasts involves interactions not only at the transcriptional level but also with protein factors involved in determining the stability and the degradation of RNA.

Blotting, Northern↗
PubMed1996

Structural basis of RNA folding and recognition in an AMP-RNA aptamer complex.

The catalytic properties of RNA and its well known role in gene expression and regulation are the consequence of its unique solution structures. Identification of the structural determinants of ligand recognition by RNA molecules is of fundamental importance for understanding the biological functions of RNA, as well as for the rational design of RNA Sequences with specific catalytic activities. Towards this latter end, Szostak et al. used in vitro selection techniques to isolate RNA sequences ('aptamers') containing a high-affinity binding site for ATP, the universal currency of cellular energy, and then used this motif to engineer ribozymes with polynucleotide kinase activity. Here we present the solution structure, as determined by multidimensional NMR spectroscopy and molecular dynamics calculations, of both uniformly and specifically 13C-, 15N-labelled 40-mer RNA containing the ATP-binding motif complexed with AMP. The aptamer adopts an L-shaped structure with two nearly orthogonal stems, each capped proximally by a G x G mismatch pair, binding the AMP ligand at their junction in a GNRA-like motif.

Adenosine Monophosphate↗
PubMed1996

A study of the contribution of changes in the cerebral blood volume to the haemodynamic response to anoxia in rat brain.

A susceptibility contrast agent which does not pass into the extra-cellular space was used to study the effect of changes in the relative cerebral blood volume (CBV) on the haemodynamic response to anoxia, for both normal and ischaemic brain tissue, in a rat model of acute focal ischaemia. In non-ischaemic tissue a strong CBV component was observed in the haemodynamic response, both during and after anoxia. During anoxia the change in the CBV of the non-ischaemic tissue was estimated to be 40% in the caudate putamen and 70% in the frontal-parietal cortex. For severely ischaemic tissue (ischaemic caudate putamen) there was no change in the CBV during anoxia while in areas of moderate ischaemia (ischaemic frontal parietal cortex) a change of 20% was observed. The effect of the contrast agent on spin-echo images was consistent with a small reduction in the microvascular blood volume of the ischaemic tissue.

Animals↗
PubMed1996

Extremely-low-frequency magnetic fields disrupt rhythmic slow activity in rat hippocampal slices.

Several studies have indicated that weak, extremely-low-frequency (ELF; 1-100 Hz) magnetic fields affect brain electrical activity and memory processes in man and laboratory animals. Our studies sought to determine whether ELF magnetic fields could couple directly with brain tissue and affect neuronal activity in vitro. We used rat hippocampal slices to study field effects on a specific brain activity known as rhythmic slow activity (RSA), or theta rhythm, which occurs in 7-15 s bursts in the hippocampus during memory functions. RSA, which, in vivo, is a cholinergic activity, is induced in hippocampal slices by perfusion of the tissue with carbachol, a stable analog of acetylcholine. We previously demonstrated that the free radical nitric oxide (NO), synthesized in carbachol-treated hippocampal slices, lengthened and destabilized the intervals between successive RSA episodes. Here, we investigate the possibility that sinusoidal ELF magnetic fields could trigger the NO-dependent perturbation of the rate of occurrence of the RSA episodes. Carbachol-treated slices were exposed for 10 min epochs to 1 or 60 Hz magnetic fields with field intensities of 5.6, 56, or 560 microT (rms), or they were sham exposed. All exposures took place in the presence of an ambient DC field of 45 microT, with an angle of -66 degrees from the horizontal plane. Sinusoidal 1 Hz fields at 56 and 560 microT, but not at 5.6 microT, triggered the irreversible destabilization of RSA intervals. Fields at 60 Hz resulted in similar, but not statistically significant, trends. Fields had no effects on RSA when NO synthesis was pharmacologically inhibited. However, field effects could take place when extracellular NO, diffusing from its cell of origin to the extracellular space,was chelated by hemoglobin. These results suggest that ELF magnetic fields exert a strong influence on NO systems in the brain; therefore, they could modulate the functional state of a variety of neuronal ensembles.

Animals↗
PubMed1996

Mechanical vibration in "double-wound" magnetic field exposure coils.

It has been suggested that "double-wound" (bifilar) exposure coils are capable of producing a sham environment in which hum and vibration will be "similar" to the field-exposed condition. We found by direct measurements in a bifilar coil system that vibration amplitude in sham and exposed conditions differed by a factor of 50 when our test system was driven at B = 10 mT. We also found that the normal laboratory environment can include vibrations of an intensity similar to that produced by the exposure system, although not necessarily of similar spectral distribution.

Acceleration↗
PubMed1996

Cerebrovascular changes in rats during ischemia and reperfusion: a comparison of BOLD and first pass bolus tracking techniques.

Both first pass bolus tracking of a susceptibility contrast agent and blood oxygenation level dependent (BOLD) sequences provide information on the tissue perfusion and the cerebral blood volume, but each sequence has its own particular limitations. In this article, both techniques were used to assess the cerebrovascular changes occurring in a rat model of focal cerebral ischemia with reperfusion after 2 h of ischemia. The blood oxygenation level dependent studies were performed before, during, and after 60 s of anoxia to observe the response of the tissue to a respiratory challenge. Both techniques were able to detect ischemia and reperfusion; however, first pass bolus tracking provided better sensitivity and was easier to interpret. Because the blood oxygenation level dependent sequence did not provide any additional information, bolus tracking would appear to be the method of choice for studies of cerebral ischemia with reperfusion.

Animals↗
PubMed1996

Follow-up of chronic thoracic aortic dissection: comparison of transesophageal echocardiography and magnetic resonance imaging.

Because survivors of thoracic aortic dissection require follow-up to detect prognostic factors such as intimal tears, persistent flow in the false lumen, and complications associated with grafts, we compared transesophageal echocardiography (TEE) with magnetic resonance imaging (MRI) prospectively in 14 patients 1 year after their initial examination. Residual dissection was identified by both techniques in 11 patients. Flow and/or thrombus in the false lumen were detected by TEE in 10 (91 %) and 6 (55%) patients, respectively, and by MRI in 9 (82%) and 5 (45%), respectively (p = NS); more tears were detected by TEE (2.5 +/- 1.4 per patient vs 0.2 +/- 0.4; p < 0.005). Satisfactory delineation of a graft in the ascending aorta was noted in all 8 (100%) of the surgically treated patients by TEE compared with 4 (50%) by MRI (p < 0.005). The upper ascending aorta was visualized clearly in fewer patients by TEE than by MRI (7 [50%] vs 13 [93%]; p < 0.05), as were the origins of the head and neck vessels (10 [71%] vs 13 [93%], p = NS). We conclude that TEE and MRI are both suitable techniques for the follow-up of patients with aortic dissection. TEE is more sensitive in identifying prognostic factors. MRI has a complementary role, particularly in visualization of the upper ascending aorta and the head and neck vessels.

Adult↗
PubMed1996

Comparison of MR perfusion imaging and microsphere measurements of regional cerebral blood flow in a rat model of middle cerebral artery occlusion.

The purpose of this investigation was to correlate magnetic resonance (MR) perfusion measurements with absolute regional cerebral blood flow (rCBF) in a rat model of focal ischemia. The MR perfusion measurements were made using dynamic first-pass bolus tracking of a susceptibility contrast agent, whereas rCBF was measured using radioactive microspheres. Two simple MR perfusion parameters, the maximum change in R2* (m delta R2*) and time delay to m delta R2* (t delta R2*), were derived from the signal intensity versus time curves on a pixel-to-pixel basis, without applying curve-fitting procedures or tracer kinetic theory. In each hemisphere, m delta R2* and t delta R2* were compared with the rCBF measurements in four selected regions of interest. Sixteen MR bolus tracking series were performed in 12 rats with occlusion of the middle cerebral artery. In all of the individual series there was a significant correlation (.0001 < or = p < or = .02) between m delta R2* and the microsphere rCBF measurements, with correlation coefficients ranging from .784 to .983. Pooling the m delta R2* data resulted in a correlation coefficient of .809 (p = .0001). There was a nonlinear correlation between the t delta R2* and rCBF. For both parameters there was considerable variation between different measurements regarding both the slope of the regression line and its intercept with the y-axis. Our results justify the use of m delta R2* as a relative measure of perfusion during acute cerebral ischemia. Because of the interindividual variation, calibration of MR perfusion measurements for the estimation of absolute flow values must be considered unreliable. The t delta R2* may have physiological relevance as a marker of collateral flow.

Animals↗