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Biomedical subjects

T Jones

Publications and source records attributed to T Jones.

At least 235 records · Page 13Linked to original sources
PubMed1996

Comparison of an antifungal agent used alone with an antifungal used with a topical steroid in inflammatory tinea pedis.

The efficacy and safety of monotherapy with oxiconazole nitrate cream, 1 percent, a topical broadspectrum antifungal agent, were compared with those of combination therapy with oxiconazole nitrate cream, 1 percent, and fluticasone propionate cream, 0.05 percent, in a multicenter, randomized, double-blind, vehicle-controlled, parallel-group study of patients with inflammatory tinea pedis. Both combination therapy and monotherapy were associated with significantly greater proportions of mycologic and clinical cure, and a better global response than vehicle. An unexpected finding in this study was that more than 70 percent of patients with interdigital tinea pedis also had plantar or plantar plus vesiculobullous infection.

Administration, Topical↗
PubMed1996

In vitro lymphocyte proliferative responses and gamma-interferon production as measures of cell-mediated immunity of cattle exposed to Pasteurella haemolytica.

Cell-mediated immune mechanisms may play a role in the pathogenesis and prevention of pneumonia in cattle caused by Pasteurella haemolytica serotype A1. To determine the circumstances required to stimulate and identify cell-mediated immune responses, calves were vaccinated with a commercial P. haemolytica bacterin or a live commercial P. haemolytica vaccine, or were infected intratracheally with virulent P. haemolytica. All calves were challenge-exposed intratracheally with P. haemolytica 31 d after vaccination or prior infection. Peripheral blood mononuclear cells and mediastinal and superficial cervical lymph node cells were stimulated with antigens prepared from P. haemolytica to evaluate in vitro proliferative responses and gamma-interferon production as measures of cell-mediated immunity. Strong proliferative responses and gamma-interferon production were detected in lymph node cells from calves vaccinated with the live vaccine and from infected calves, especially in response to stimulation with an outer membrane protein preparation from P. haemolytica. Greater proliferative responses and gamma-interferon production were associated with the lymph node nearer the site of bacterin administration (superficial cervical lymph node) or the site of infection (mediastinal lymph node), whereas greater proliferative responses and gamma-interferon production were associated with the more distant lymph node (mediastinal lymph node) in calves vaccinated with the live vaccine. Neither proliferative responses nor gamma-interferon production were detected in peripheral blood mononuclear cells from calves that were vaccinated for or infected with P. haemolytica. Antileukotoxin antibody titers were determined by a serum neutralization assay, and protection against pneumonic lesions was more closely correlated with antileukotoxin antibody responses than with lymphocyte proliferation or gamma-interferon responses.

Animals↗
PubMed1996

Guided bone regeneration to facilitate implant and prosthodontic therapy: three case reports.

In some patients, lack of bone at a desired fixture site has resulted, by necessity, in the placement of endosseous implants in less than favorable locations. The principles of guided bone regeneration can be used to restore lost alveolar bone and permit the placement of implants at more ideal locations, or to provide a more favorable ridge form to support a removable prosthesis. The advantages of a two-stage technique involving bone grafting followed by a healing period prior to implant placement are discussed. Different methods of membrane tenting to provide space for bone growth are illustrated by three case reports. Evidence of bone augmentation is provided by computed tomography.

Adult↗
PubMed1995

Hyperpnoea during and immediately after exercise in man: evidence of motor cortical involvement.

1. The neurophysiological basis for the increase in breathing associated with exercise remains obscure. The present study uses positron emission tomography (PET) to measure relative regional cerebral blood flow (rCBF) in order to identify sites of increased neuronal activation during and immediately following exercise. 2. Male volunteers underwent H2(15)O PET scanning during two complementary studies. Firstly, six subjects performed right leg exercise, adequate to increase oxygen uptake 2.5-fold. Secondly, five different subjects were scanned immediately following bicycle exercise (adequate to increase oxygen uptake 5-fold) while breathing was still increased. In each study, as a control, scanning was also performed during matched passive isocapnic positive pressure ventilation; additionally, in the first study, passive right leg movement was performed. 3. Increases in relative rCBF were obtained in each individual and co-registered with their magnetic resonance image of the brain defining individual gyral morphology. 4. During exercise, individual and group analysis revealed significant relative rCBF increases in the left and right superomedial primary motor cortex (the motor cortical 'leg' areas) and also in the left and right superolateral primary motor cortex in areas previously shown to be associated with volitional breathing. After exercise, there was no significant increase in relative rCBF in the superomedial areas but such increases were still present bilaterally in the superolateral areas which had been activated during the exercise. Other relative rCBF increases were also found, both during and after exercise, in cortical and subcortical areas known to be involved in motor control. 5. The results from PET scans during and after exercise, taken together, provide evidence for motor cortical involvement in the exercise-related hyperpnoea in man.

Adult↗
PubMed1995

Famciclovir for the treatment of acute herpes zoster: effects on acute disease and postherpetic neuralgia. A randomized, double-blind, placebo-controlled trial. Collaborative Famciclovir Herpes Zoster Study Group.

OBJECTIVE: To document the effects of treatment with famciclovir on the acute signs and symptoms of herpes zoster and postherpetic neuralgia. DESIGN: A randomized, double-blind, placebo-controlled, multicenter trial. SETTING: 36 centers in the United States, Canada, and Australia. PATIENTS: 419 immunocompetent adults with uncomplicated herpes zoster. INTERVENTION: Patients were assigned within 72 hours of rash onset to famciclovir, 500 mg; famciclovir, 750 mg; or placebo, three times daily for 7 days. MEASUREMENTS: Lesions were assessed daily for as long as 14 days until full crusting occurred and then weekly until the lesions healed. Viral cultures were obtained daily while vesicles were present. Pain was assessed at each of the visits at which lesions were examined and then monthly for 5 months after the lesions healed. Safety was assessed throughout the study. RESULTS: Famciclovir was well tolerated, with a safety profile similar to that of placebo. Famciclovir accelerated lesion healing and reduced the duration of viral shedding. Most importantly, famciclovir recipients had faster resolution of postherpetic neuralgia (approximately twofold faster) than placebo recipients; differences between the placebo group and both the 500-mg famciclovir group (hazard ratio, 1.7 [95% CI, 1.1 to 2.7]) and the 750-mg famciclovir group (hazard ratio, 1.9 [CI, 1.2 to 2.9]) were statistically significant (P = 0.02 and 0.01, respectively). The median duration of postherpetic neuralgia was reduced by approximately 2 months. CONCLUSIONS: Oral famciclovir, 500 mg or 750 mg three times daily for 7 days, is an effective and well-tolerated therapy for herpes zoster that decreases the duration of the disease's most debilitating complication, postherpetic neuralgia.

2-Aminopurine↗
PubMed1995

High-affinity RNA ligands to Escherichia coli ribosomes and ribosomal protein S1: comparison of natural and unnatural binding sites.

High-affinity RNA ligands were generated against intact 30S ribosomes, S1-depleted 30S ribosomes, and purified ribosomal protein S1. Sequence analysis indicated two classes of ligand: unstructured RNAs containing a Shine-Dalgarno sequence and structured RNAs containing a pseudoknot. The Shine-Dalgarno-containing ligands were generated against S1-depleted 30S ribosomes but, surprisingly, not against intact 30S ribosomes or ribosomal protein S1. In contrast, pseudoknot-containing ligands were generated against intact ribosomes as well as purified S1 protein. The two classes of ligand exhibited specificity for their respective targets, as well as conserved sequence and secondary structure reminiscent of naturally occurring, cis-acting mRNA elements.

Base Sequence↗
PubMed1995

The eukaryotic cofactor for the human immunodeficiency virus type 1 (HIV-1) rev protein, eIF-5A, maps to chromosome 17p12-p13: three eIF-5A pseudogenes map to 10q23.3, 17q25, and 19q13.2.

The eukaryotic initiation factor 5A (eIF-5A) has been identified as an essential cofactor for the HIV-1 transactivator protein Rev. Rev plays a key role in the complex regulation of HIV-1 gene expression and thereby in the generation of infectious virus particles. Expression of eIF-5A is vital for Rev function, and inhibition of this interaction leads to a block of the viral replication cycle. In humans, four different eIF-5A genes have been identified. One codes for the eIF-5A protein and the other three are pseudogenes. Using a panel of somatic rodent-human cell hybrids in combination with fluorescence in situ hybridization analysis, we show that the four genes map to three different chromosomes. The coding eIF-5A gene (EIF5A) maps to 17p12-p13, and the three pseudogenes EIF5AP1, EIF5AP2, and EIF5AP3 map to 10q23.3, 17q25, and 19q13.2, respectively. This is the first localization report for a eukaryotic cofactor for a regulatory HIV-1 protein.

Base Sequence↗
PubMed1995

Localization of an epithelial-specific receptor kinase (EDDR1) to chromosome 6q16.

A protein receptor tyrosine kinase (EDDR1) has been isolated from a complementary DNA library of SKOV-3, an epithelial ovarian cancer cell line. The primary structure of the predicted amino acid sequence of the protein shows a novel N-terminal region that has homology to a factor VIII-like domain. The C-terminal catalytic domain has all of the canonical sequence motifs of a receptor tyrosine kinase with homology to the TRK-2H protein (49%), which suggests that it is a type II receptor. It is expressed in epithelial cells of several tissues. To determine the chromosomal localization of the gene, somatic cell hybrids were analyzed by PCR amplification using oligonucleotide primers specific for EDDR1. Segregation was observed to a hybrid containing human chromosome 6. Cosmids for EDDR1 were isolated from a human chromosome 6 cosmid library and were shown by fluorescence in situ hybridization to map to 6q16.

Base Sequence↗
PubMed1995

High level expression of human leukemia inhibitory factor (LIF) from a synthetic gene in Escherichia coli and the physical and biological characterization of the protein.

LIF is a multi-functional cytokine that elicits effects on a broad range of cell types. In this report, we present the high level expression of human LIF (hLIF) from a chemically synthesized gene template in Escherichia coli where it comprises up to 25% of the cellular protein. The recombinant hLIF, after purification and folding, was examined using CD, FTIR spectroscopy and light scattering. CD and FTIR spectra showed that the hLIF is an alpha-helical protein and has a distinct tertiary structure. The IFTR spectrum resembles that of other four helical bundle proteins including G-CSF and IL-6. Light scattering analysis indicated that it is a monomeric protein, distinguishing it from M-CSF and interferon gamma, which also belong to the class of four helical bundle proteins but are dimeric. Recombinant hLIF was assayed for its activity on the murine leukemic cell line, M-1 as well as on human leukemic cell line, ML-1. It inhibited the growth of M-1 cells and differentiated them towards macrophages. However, it did not have any differentiation inducing effect on human leukemic cell lines alone or in combination with other cytokines.

Amino Acid Sequence↗
PubMed1995

Characterization of a t(10;11)(p13-14;q14-21) in the monoblastic cell line U937.

Previous analysis of the monoblastic cell line U937 has shown that several sublines contain a rearranged chromosome arm 11q. In order to determine the true nature of the rearrangement, fluorescence in situ hybridization (FISH) was carried out with various combinations of single copy anonymous markers, clones containing genes, a chromosome 10 paint, and an 11 centromere specific sequence. The rearrangement was deduced to be a reciprocal translocation between chromosomes 10 and 11 described as t(10;11)(p13-14;q14-21). The breakpoint on chromosome 11 is telomeric to the INT2 gene and the pHS11 probe at 11q13, and centromeric to the marker D11S36 localized to 11q14.3-q22.1 and the MLL gene at 11q23. Similar translocations have been reported in various acute leukemias, principally of the monocytic lineage, and also in T-cell precursor acute lymphocytic leukemias. Further characterization of the genetic rearrangements in U937 may lead to the isolation of genes important in leukemogenesis and provide an in vitro system for their study.

Chromosome Mapping↗
PubMed1995

Validation of noninvasive quantification of rCBF compared with dynamic/integral method by using positron emission tomography and oxygen-15 labeled water.

This study proposes a new solution for the quantification of rCBF pixel-by-pixel using PET and 15O-H2O. The method represents an application of weighted integration that used PET image only, requiring no input function of arterial blood. It generates the rCBF image quickly and automatically. Simulation studies revealed that the calculation of rCBF was fairly stable as long as a relatively shorter scan frame time and longer scan time were selected. Calculated images of actual PET study by this method correlated significantly with those identified by the dynamic/integral method. Because this procedure could detect whole brain CBF change between different studies as accurately as by the dynamic/integral method, this procedure may be the most suitable for brain activation studies.

Cerebrovascular Circulation↗
PubMed1995

Flow instabilities induced by coronary artery stents: assessment with an in vitro pulse duplicator.

An in vitro pulse duplicator system was used to investigate whether coronary artery stents induce downstream flow instabilities. Hot film or electrochemical probes were used to measure wall shear stress before and after deployment of both single and multiple (overlapping) stents in normal and diseased coronary geometries. Left main coronary diameters ranged from 4 to 5 mm, whereas left anterior descending (LAD) and left circumflex (LCX) diameters ranged from 2 to 4 mm. Under resting conditions, all coronary flow waveforms remained laminar, even after stent placement. However, disturbances were found downstream from a stent placed in the proximal LAD under mild exercise conditions. These disturbances were found 5 mm distal to the stent, in both the LAD and the proximal LCX. Turbulence intensities of order 5% were induced by a single slotted stent in a normal LAD geometry. In cases of distal disease, the turbulence intensity was 9% with one stent and 11% with tandem stents. In cases of proximal disease, these values were 19 and 25%, respectively. The shear stress from these disturbances (20-200 dynes cm-2) is sufficient to delay re-endothelialization and promote restenosis. Therefore, the disturbances could contribute to the increased incidence of restenosis reported with multiple stents, and with stents used in cases of diffuse coronary disease.

Aorta↗
PubMed1995

Can positron emission tomography (PET) be used to detect subclinical response to cancer therapy? The EC PET Oncology Concerted Action and the EORTC PET Study Group.

At the EORTC NCI New Drug Development Meeting in Amsterdam in 1994, a workshop, suggested by the EC PET (positron emission tomography) Oncology concerted action, was held to bring together many of those European PET centres investigating the use of [18F]FDG ([18F]2-fluoro-2 deoxyglucose) PET scanning as a measure of response to cancer therapy. Of the current 31 PET centres in Europe invited to contribute, 15 centres already had data and others expressed interest. Many of the groups were collaborating with local oncologists to measure tumour response to chemotherapy (12 groups) and radiotherapy (three groups) with this technique. Despite variations of methodology, and difficulties in data interpretation, assessment of tumour [18F]FDG uptake was thought to be a reasonable method for the functional imaging of tumours, assessing metabolic rate and providing a measure of tumour response. Broadly, pooling experience, it would appear that changes in [18F]FDG tumour uptake following one or two cycles of chemotherapy treatment was related to ultimate clinical responses. Patients showing most reduction in [18F]FDG uptake achieved the best clinical responses. Data were also available on the effect of chemotherapy on normal tissues and some data on the effect of radiotherapy and tumour response. It was concluded that changes in [18F]FDG uptake as measured with PET may provide useful information on clinical as well as subclinical response of tumours to anticancer therapy. This could be useful as a guide to early response to therapy as well as providing functional assessment of residual masses of disease. More specific markers of cellular proliferation e.g. [11C]thymidine, or [11C]- amino acids may provide even more accurate information. A strategy was outlined whereby PET scanning protocols could parallel EORTC early clinical trials so that [18F]FDG response information could supplement phase I and II clinical studies. Following these developments, an EORTC study group was formed under the auspices of the EORTC research branch, and the strategy for future development in Europe outlined.

Clinical Trials, Phase I as Topic↗
PubMed1995

Benzodiazepine receptor quantification in vivo in humans using [11C]flumazenil and PET: application of the steady-state principle.

Carbon-11-labeled flumazenil combined with positron emission tomography (PET) was used to measure the concentration (Bmax) of the benzodiazepine (Bz) receptor in the brain and its equilibrium dissociation constant (KD) for flumazenil in five normal subjects. The steady-state approach was used injecting the tracer as a bolus of high specific activity. In each subject two studies were carried out. The first study was performed at essentially zero receptor occupancy, the tracer alone study. The second study was performed at a steady-state receptor occupancy of about 50%, achieved by a prolonged constant infusion of nonlabeled ("cold") flumazenil starting 2h before the bolus tracer injection and continuing until the end of scanning period. In this second study the free concentration of unmetabolized flumazenil in plasma water was measured in multiple blood samples. The observed tissue and plasma tracer curves, calibrated in the same units of radioactivity per millimeter, were analyzed in two ways: (a) by the noncompartmental (stochastic) approach making no assumptions regarding number of compartments in the tissue, and (b) by the single-compartment approach assuming rapid exchange (mixing) of tracer between all tissue compartments. The noncompartmental and the compartmental analyses gave essentially the same values for the distribution volume of the tracer, the parameter used for quantitation of the Bz receptor. As the compartmental approach could be applied to a shorter observation period (60 min instead of 120 min) it was preferred. The five subjects had a mean KD value of 12 nM/L of water and Bmax values of the grey matter ranging from 39 +/- 11 in thalamus to 120 +/- 14 nM/L of brain in occipital cortex. Most previous studies have been based on the pseudoequilibrium approach using the brain stem as a receptor-free reference region. This yields practically the same KD but lower Bmax values than the steady-state approach presented here.

Adult↗
PubMed1995

Hyperdynamic performance of remote myocardium in acute infarction. Correlation between regional contractile function and myocardial perfusion.

During and after myocardial infarction (MI), compensatory contractile and structural changes taking place in the remote uninvolved myocardial regions have been well described, in both experimental and clinical settings. However, quantitative information on the changes in perfusion in these regions in relation to their altered contractile function have not been available. This study was designed to assess the in vivo relationship between contractile function and perfusion in remote uninvolved hypercontractile myocardial regions, subtended by angiographically normal coronary arteries in patients with MI and single-vessel coronary artery disease. We utilized two-dimensional echocardiography and 15O-water positron emission tomography imaging to assess regional contractile function and myocardial blood flow, respectively. Measurements were performed in nine patients with single-vessel coronary artery disease and angiographically confirmed recanalization of the infarct-related artery, 1-2 days after MI (group A). Only patients demonstrating severely impaired wall motion of the infarcted area and reactive hypercontractility of the remote uninvolved regions were enrolled. Seven patients with previous non-reperfused MI (6-8 months post-MI) served as a control (group B). Systolic wall thickening and regional myocardial blood flow data sets were created for the remote myocardial segments perfused by angiographically detected patent coronary arteries by assigning regions on the tomograms to equivalent echocardiographic segments. In the remote regions, wall thickening and regional myocardial blood flow were higher in group A patients by 26% (43 +/- 6% vs 34 +/- 4%; P = 0.005) and 20% (1.06 +/- 0.15 vs 0.89 +/- 0.06 ml.g-1 per minute; P = 0.019), respectively. For both groups of patients, a significant correlation (r = 0.67; P = 0.004) between systolic wall thickening and regional myocardial blood flow was obtained. Infarcted regions in both groups showed no systolic wall thickening. In this selected group of patients these data demonstrate: (1) a proportionate increase in contractility and regional myocardial blood flow in uninvolved territories in patients with recent and old MI; (2) the in vivo relationship between contractile function and myocardial perfusion in man in these regions. When infarcted zones in both groups are equally affected, enhanced levels of catecholamines and sympathetic drive as well as different loading conditions may account for the hyperkinetic performance and consequently for the increased perfusion level in uninvolved segments in patients with recent MI.

Adult↗
PubMed1995

Transcriptional activation of the nitrogenase promoter in vitro: adenosine nucleotides are required for inhibition of NIFA activity by NIFL.

The enhancer-binding protein NIFA is required for transcriptional activation of nif promoters by the alternative holoenzyme form of RNA polymerase, which contains the sigma factor sigma 54 (sigma N). NIFA hydrolyzes nucleoside triphosphates to catalyze the isomerization of closed promoter complexes to transcriptionally competent open complexes. The activity of NIFA is antagonized by the regulatory protein NIFL in response to oxygen and fixed nitrogen in vivo. We have investigated the requirement for nucleotides in the formation and stability of open promoter complexes by NIFA and inhibition of its activity by NIFL at the Klebsiella pneumoniae nifH promoter. Open complexes formed by sigma 54-containing RNA polymerase are considerably more stable to heparin challenge in the presence of GTP than in the presence of ATP. This differential stability is most probably a consequence of GTP being the initiating nucleotide at this promoter. Adenosine nucleosides are specifically required for Azotobacter vinelandii NIFL to inhibit open complex formation by native NIFA, and the nucleoside triphosphatase activity of NIFA is strongly inhibited by NIFL under these conditions. We propose a model in which NIFL modulates the activity of NIFA via an adenosine nucleotide switch.

Acid Anhydride Hydrolases↗
PubMed1995

Innervation of motoneurons based on dendritic orientation.

1. The distribution of terminals from vestibulospinal (VS) axons on the dendritic trees of neck motoneurons was determined by combining the anterograde transport of Phaseolus Vulgaris Leucoagglutinin (PHA-L) with intracellular staining techniques and three-dimensional reconstruction methods. 2. Contacts between VS axon terminals and dendrites were arranged in a nonuniform pattern that depended on the orientation (i.e., rostro-caudal vs. dorsolateral) of the dendrites. 3. This innervation pattern satisfies a critical structural condition necessary for selective nonlinear interactions between pairs of simultaneously active inputs to motoneurons.

Animals↗