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Biomedical subjects

T Jones

Publications and source records attributed to T Jones.

At least 343 records · Page 19Linked to original sources
PubMed1990

The nigrostriatal dopaminergic system assessed in vivo by positron emission tomography in healthy volunteer subjects and patients with Parkinson's disease.

A group of healthy control subjects and patients with Parkinson's disease were investigated using positron emission tomography and two tracers as indicators of different specific properties of the presynaptic dopaminergic system in caudate nucleus and putamen. The first tracer, 6-L-(18F)-fluorodopa, was used as an analog of levodopa to assess its regional brain uptake, conversion into, and retention as dopamine and further metabolites. The second tracer, (11C)-nomifensine was employed as an indicator of striatal monaminergic reuptake sites that are principally dopaminergic. We have used this tracer to assess dopaminergic nerve terminal density. In patients with Parkinson's disease, striatal uptake of both tracers was decreased, putamen being significantly more affected than caudate. Side-to-side differences of uptake in putamen, but not caudate, correlated with corresponding left-right differences of scored clinical motor performance. Both 6-L(18F)-fluorodopa and (11C)-nomifensine tracer uptake in putamen was decreased on average to 40% of normal values, suggesting that a substantial part of the cellular elements of the dopaminergic nigrostriatal system is still intact in living parkinsonian patients. This is in contrast to the generally extreme depletion of endogenous dopamine in the putamen of patients found at postmortem. Our results lend support to the search for drug treatments that protect against further nigrostriatal cell loss and that could be exhibited as soon as the disease manifests clinically. If successful, a sufficient striatal nerve terminal pool would remain so that the effectiveness of levodopa as a dopamine repletor could persist.

Aged↗
PubMed1990

The effects of cued UCS rehearsal on the retention of differential 'fear' conditioning: an experimental analogue of the 'worry' process.

This study describes a human electrodermal conditioning experiment in which subjects were asked to mentally rehearse the UCS in a period following initial fear conditioning and prior to a test period involving nonreinforced presentations of the CS. Subjects who were asked to rehearse the UCS retained a differential fear CR during subsequent unreinforced presentations of the CS, but control subjects who were asked to rehearse either a nonaversive event or an aversive event unrelated to the UCS failed to retain the differential CR they had acquired during conditioning. These results suggest that rehearsal of the UCS during periods when CS and UCS are absent can aid the persistence of a fear CR in the absence of further pairings of the CS and UCS. It is argued that these effects can be explained in terms of the effect of UCS rehearsal on the strength and evaluation of the UCS representation. It is also suggested that cued UCS rehearsal might provide a useful procedure for understanding clinical incubation effects and for understanding how the 'worry' process contributes to the maintenance and incubation of fear.

Adolescent↗
PubMed1990

Stereospecific synthesis, assignment of absolute configuration, and biological activity of the enantiomers of 3-[[[3-[2-(7-chloroquinolin-2-yl)-(E)-ethenyl]phenyl] [[3-(dimethylamino)-3-oxopropyl]thio]methyl]thio]propionic acid, a potent and specific leukotriene D4 receptor antagonist.

The enantiomers of the leukotriene D4 antagonist 3-[[[3-[2-(7-chloroquinolin-2-yl)-(E)-ethenyl]phenyl] [[3-(dimethylamino)-3-oxopropyl]thio]methyl]thio]propionic acid (L-660,711)(MK-571) have been prepared, their absolute stereochemistry has been assigned as S for (+)-1 and R for (-)-1 by X-ray analysis of a synthetic intermediate (5), and the biological activity of the enantiomers has been explored. Unexpectedly, the enantiomers are both comparably biologically active with (+)-1 slightly more intrinsically active at the LTD4 receptor in vitro.

Animals↗
PubMed1990

Combination of dynamic and integral methods for generating reproducible functional CBF images.

A new method to measure regional CBF is presented, applying both dynamic and integral analyses to a dynamic sequence of positron emission tomographic scans collected during and following the administration of H2(15)O (inhalation of C15O2). The dynamic analysis is used to correct continuously monitored arterial whole-blood activity for delay and dispersion relative to tissue scans. An integral analysis including corrections for this delay and dispersion is then used to calculate CBF on a pixel-by-pixel basis. Normal values and reproducibility over a 2-h period are presented, together with the results of validation and simulation studies. The results indicate that the single-tissue compartment model adequately describes the distribution of H2(15)O in the brain, without recourse to postulating a nonexchanging water pool.

Carbon Radioisotopes↗
PubMed1990

A two-compartment description and kinetic procedure for measuring regional cerebral [11C]nomifensine uptake using positron emission tomography.

S-[11C]Nomifensine (S-[11C]NMF) is a positron-emitting tracer suitable for positron emission tomography, which binds to both dopaminergic and noradrenergic reuptake sites in the striatum and the thalamus. Modelling of the cerebral distribution of this drug has been hampered by the rapid appearance of glucuronide metabolites in the plasma, which do not cross the blood--brain barrier. To date, [11C]NMF uptake has simply been expressed as regional versus nonspecific cerebellar activity ratios. We have calculated a "free" NMF input curve from red cell activity curves, using the fact that the free drug rapidly equilibrates between red cells and plasma, while glucuronides do not enter red cells. With this free [11C]NMF input function, all regional cerebral uptake curves could be fitted to a conventional two-compartment model, defining tracer distribution in terms of [11C]NMF regional volume of distribution. Assuming that the cerebellar volume of distribution of [11C]NMF represents the nonspecific volume of distribution of the tracer in striatum and thalamus, we have calculated an equilibrium partition coefficient for [11C]NMF between freely exchanging specific and nonspecific compartments in these regions, representing its "binding potential" to dopaminergic or noradrenergic uptake sites (or complexes). This partition coefficient was lower in the striatum when the racemate rather than the active S-enantiomer of [11C]NMF was administered. In the striatum of patients suffering from Parkinson's disease and multiple-system atrophy, the specific compartmentation of S-[11C]NMF was significantly decreased compared with that of age-matched volunteers.

Brain↗
PubMed1990

Positron emission tomography.

While positron emission tomography (PET) represents the most advanced methodology using radiotracers, it is subject to two main constraints. The first is the physical accuracy with which the regional distribution, time course and concentration of the tracer can be determined. This is principally a function of the instrumentation. The second constraint is the biological accuracy, that a chosen tracer molecule defines the specific biological pathway under study. This paper discusses the application of PET, mainly to the brain, and future possible improvements to this powerful technique.

Brain↗
PubMed1990

Conditional immortalization of human thyroid epithelial cells: a tool for analysis of oncogene action.

To overcome the difficulty of assessing oncogene action in human epithelial cell types, such as thyroid, which have limited proliferative potential in culture, we have explored the use of temperature-sensitive (ts) mutants of simian virus 40 (SV40) early region to create conditionally immortalized epithelial cell lines. Normal primary cultures of human thyroid follicular cells were transfected with a plasmid containing the SV40 early region from mutant tsA58. Expanding epithelial colonies were observed after 2 to 3 months, all of which grew to greater than 200 population doublings without crisis. All showed tight temperature dependence for growth. After switch-up to the restrictive temperature (40.5 degrees C), no further increase in cell number was seen after 1 to 2 days. However, DNA synthesis declined much more slowly; the dissociation from cell division led to marked polyploidy. Viability was maintained for up to 2 weeks. Introduction of an inducible mutant ras gene into ts thyroid cells led, as expected, to morphological transformation at the permissive temperature when ras was induced. Interestingly, this was associated with a marked reduction in net growth rate. At the restrictive temperature, induction of mutant ras caused rapid cell death. These results demonstrate the utility of a ts SV40 mutant to permit the study of oncogene action in an otherwise nonproliferative target cell and reveal important differences in the interaction between ras and SV40 T in these epithelial cells compared with previously studied cell types.

Animals↗
PubMed1990

Chlamydia: management in the physician's office.

Chlamydia trachomatis infections constitute the most prevalent bacterial sexually transmitted disease (STD) in Wisconsin. In 1987, chlamydia became Wisconsin's most frequently reported STD. Several significant clinical syndromes have been associated with chlamydia infection. Prevention and control of STD needs to become a basic part of primary care within the private medical setting. Determination of the need to test a patient for chlamydia infection cannot be based solely on the presence of signs or symptoms. Physicians in private practice need to identify high-risk patients and selectively screen high-risk men and women, rapidly initiate treatment of chlamydia-infected patients and their sexual partners, and work closely with public health personnel as part of disease intervention.

Chlamydia Infections↗
PubMed1989

PET scanning.

Explore the source record for details and available documents.

Brain↗
PubMed1989

Quality control procedures in positron tomography.

The derivation of physiological parameters in positron tomography relies on accurate calibration of the tomograph. Normally, the calibration relates image pixel count density to the count rate from an external blood counter per unit activity concentration in each device. The quality control of the latter is simple and relies on detector stability assessed by measurement of a standard source of similar geometry to a blood sample. The quality control of the tomographic data depends on (i) detector stability, (ii) uniformity of calibration and normalisation sources and (iii) reproducibility of the attenuation correction procedure. A quality control procedure has been developed for an 8 detector ring (15 transaxial plane) tomograph in which detector response is assessed by acquiring data from retractable transmission ring sources. These are scanned daily and a print out of detector efficiencies is produced as well as changes from a given date. This provides the raw data from which decisions on recalibration or renormalization are made.

Quality Control↗
PubMed1989

Aspects of three dimensional reconstruction for a multi ring positron tomograph.

An important feature of multi ring positron tomographs is the inter plane septa, the purpose of which is to reduce random and scattered coincidences. In general, such septa also eliminate the coincidence lines of response between pairs of detectors more than one ring apart. The operation of a camera without septa must result in an increase not only in the true coincidence rate, but also in the singles, and therefore in the dead time and randoms rate, and in the scattered coincidences. A configuration option in the coincidence hardware of the 8 ring, 15 slice ECAT 931/08-12 enables a full set of 64 sinograms to be acquired when the septa are removed. The detector normalisation and transmission data for studies with the septa out can be obtained using a rotating pin source. To take maximum advantage of the additional signal, the emission data must be reconstructed using a fully three dimensional reconstruction algorithm. This paper presents an analysis of some phantom studies acquired without septa and reconstructed in three dimensions. The results are compared with data acquired with septa for the same phantoms imaged under similar conditions. It is found that, with the septa removed, the signal to noise for a uniform, 20 cm diameter cylinder improves by a factor of 2.8 in the centre of the field of view, whereas in regions distant from the centre in the axial direction, the signal to noise decreases due to the increase in scatter and randoms. An improvement in signal to noise is observed in 6 cm of the 10 cm axial length of the tomograph.

Image Processing, Computer-Assisted↗
PubMed1989

Immune restoration with interleukin-2 in patients with squamous cell carcinoma of the head and neck.

Patients with head and neck squamous cell carcinoma commonly have depressed cell-mediated immunity which is known to correlate with ultimate prognosis. Selective immune studies were conducted in 27 head and neck cancer patients to determine the potential of interleukin-2 as an immune restorative agent. Patients showed the expected depression of lymphocyte proliferation to phytohemagglutinin and had borderline depressed natural killer cell activity and relatively normal interleukin-2 production. Addition of interleukin-2 at 100 units/ml markedly enhanced natural killer cell activity to normal levels. Serum from head and neck patients was also immune-suppressive. Heat-inactivated serum depressed lymphocyte proliferation and natural killer cell activity of control leukocytes. Lymphocyte incubation with interleukin-2 significantly counteracted immune suppressive serum effects and restored depressed lymphocyte function to normal levels. The effective in vitro interleukin-2 dose is potentially achievable by infusion at approximate doses of 3 X 10(6) units/M2.

Adult↗
PubMed1989

Characterisation of human thyroid epithelial cells immortalised in vitro by simian virus 40 DNA transfection.

Human primary thyroid follicular epithelial cells were transfected with a plasmid containing an origin-defective SV40 genome (SVori-) to produce several immortal cell lines. Two of the 10 cell lines analysed expressed specific features of thyroid epithelial function (iodide-trapping and thyroglobulin production). These two lines were characterised in detail and found to be growth factor-independent, capable of anchorage-independent growth at low frequency but non-tumorigenic in nude mice. These differentiated, These differentiated, partially transformed cell lines were shown to be suitable for gene transfer at high frequency using simple coprecipitation techniques.

Adult↗