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T Jones

Publications and source records attributed to T Jones.

At least 73 records · Page 4Linked to original sources
PubMed2001

Rotavirus vaccine AVANT/GlaxoSmithKline.

AVANT Immunotherapeutics (formerly Virus Research Institute) and GlaxoSmithKline are developing a live oral rotavirus vaccine with potential to elicit a broadly-protective immune response against the most prevalent strains of rotavirus. Following successful completion of a phase II clinical efficacy trial in June 1999, SmithKline Beecham (now GlaxoSmithKline) assumed responsibility for all subsequent clinical and other development activities [328635], [333677]. Following a licensing agreement, the vaccine was refined and renamed RIX-4414 [371713]. In May 2000, AVANT reported the results of a second-year surveillance extension of the phase II study. The results suggested that AVANT's two-dose oral rotavirus vaccine should be helpful in preventing rotavirus gastroenteritis (RGE) disease in young children for at least two years following administration [365202]. In March 2000, SmithKline Beecham reported that it had initiated phase I/II bridging studies in Europe and the company planned to start phase III safety and efficacy studies in 2001 after review with the health authorities [358963]. In October 2000, Dain Rauscher Wessels stated that an estimated market penetration of 30 to 40% suggested potential sales in excess of US $500 million pa. As a result, the analysts also estimated that incremental revenues to AVANT could be over US $50 million pa [411122].

Administration, Oral↗
PubMed2000

Prevalence of small inversions in yeast gene order evolution.

Gene order evolution in two eukaryotes was studied by comparing the Saccharomyces cerevisiae genome sequence to extensive new data from whole-genome shotgun and cosmid sequencing of Candida albicans. Gene order is substantially different between these two yeasts, with only 9% of gene pairs that are adjacent in one species being conserved as adjacent in the other. Inversion of small segments of DNA, less than 10 genes long, has been a major cause of rearrangement, which means that even where a pair of genes has been conserved as adjacent, the transcriptional orientations of the two genes relative to one another are often different. We estimate that about 1,100 single-gene inversions have occurred since the divergence between these species. Other genes that are adjacent in one species are in the same neighborhood in the other, but their precise arrangement has been disrupted, probably by multiple successive multigene inversions. We estimate that gene adjacencies have been broken as frequently by local rearrangements as by chromosomal translocations or long-distance transpositions. A bias toward small inversions has been suggested by other studies on animals and plants and may be general among eukaryotes.

Candida albicans↗
PubMed2000

Thalamic microglial activation in ischemic stroke detected in vivo by PET and [11C]PK1195.

Using quantitative PET, the authors studied the binding of [11C]PK11195, a marker of activated microglia, in the thalamus of patients with chronic middle cerebral artery infarcts. All patients showed increased [11C]PK11195 binding in the ipsilateral thalamus, indicating the activation of microglia in degenerating projection areas remote from the primary lesion. A persistent increase in [11C]PK11195 binding suggests active, long-term thalamic microstructural changes after corticothalamic connection damage.

Adult↗
PubMed2000

Cushing's disease: clinical manifestations and diagnostic evaluation.

The most common endogenous cause of Cushing's syndrome is Cushing's disease. Frequent clinical findings include weight gain, truncal obesity, striae, hypertension, glucose intolerance and infections. Cranial nerve II may be affected by enlarging pituitary adenomas in Cushing's disease; cranial nerves III, IV and VI may also be affected. The evaluation of patients with suspected Cushing's disease and syndrome requires an understanding of the proper use and limitations of the tests commonly included in the diagnostic work-up. The best screening test for Cushing's syndrome is a 24-hour urine collection with analysis for urinary free cortisol excretion. Low-dose and high-dose dexamethasone suppression tests, corticotropin assays, a corticotropin-releasing hormone stimulation test and inferior petrosal sinus catheterization may be required for a definitive diagnosis. Magnetic resonance imaging is useful in localizing the lesion. Surgical removal of the lesion by a transphenoidal approach is usually successful, but long-term follow-up is required. Some patients require lifetime glucocorticoid replacement therapy.

Adenoma↗
PubMed2000

Evaluation of the hygienic performances of the processes for cleaning, dressing and cooling pig carcasses at eight packing plants.

The hygienic performances of the processes for the production of cooled carcasses at eight pork packing plants were assessed from small sets of microbiological data. At each plant, a single sample was obtained from a randomly selected site on each of 25 randomly selected carcasses at each of three stages of processing, which were after polishing, after washing at the end of the dressing process, and after cooling. The aerobic bacteria, coliforms and Escherichia coli recovered from each sample were enumerated. When bacteria of one type were recovered from > or = 20 of 25 samples, the log mean number of those bacteria on the population of carcasses undergoing processing was estimated on the assumption that the set of counts was normally distributed. The log of the total number recovered from 25 samples was calculated for each set of counts. The log mean numbers of total aerobic bacteria recovered from the polished carcasses at different plants ranged from about 1.9 to 3.8 log cfu cm(-2). At six of the plants, the log mean numbers of total aerobes on the cooled carcasses did not differ substantially from the log mean numbers on the polished carcasses, but the log mean numbers on the cooled carcasses were substantially higher at one plant and substantially lower at another than on the polished carcasses. Coliforms and E. coli were recovered from too few samples in most sets from cooled carcasses for estimation of their log mean numbers. However, the log total numbers of coliforms and E. coli recovered indicated that substantial numbers of those organisms were added to carcasses during the dressing processes at four of the plants, and that the numbers on the carcasses were substantially reduced by the processes for cooling without spraying at two of the plants. At seven of the plants, the total numbers of coliforms and E. coli recovered from cooled carcasses were <3.1 and <2.2 log cfu 2500 cm(-2), respectively. The findings indicate that production processes for pig carcasses can be operated to give cooled carcasses with log mean numbers of total aerobes < 2 cm(-2), and log total numbers of coliforms and E. coli each < 1 2500 cm(-2).

Animals↗
PubMed2000

Modulation of fluorouracil tissue pharmacokinetics by eniluracil: in-vivo imaging of drug action.

BACKGROUND: Fluorouracil is widely used for chemotherapy of gastrointestinal cancer, but response rates are poor. Eniluracil is being developed as an inactivator of dihydropyrimidine dehydrogenase, the enzyme that brings about first-pass degradation of fluorouracil. We studied the mechanism of action of eniluracil by measuring with positron emission tomography (PET) the effect of eniluracil on tumour and normal-tissue pharmacokinetics of fluorine-18-labelled fluorouracil. METHODS: Six patients with advanced gastrointestinal cancers were studied. PET scanning was done after injection of oxygen-15-labelled water to assess tissue blood flow, followed by 1 mg/m2 18F-fluorouracil. We compared the pharmacokinetics of 18F-fluorouracil when the patients had not received eniluracil, during a 4-day course of oral eniluracil, and during a 28-day course of oral fluorouracil plus eniluracil. FINDINGS: In eniluracil-naïve patients, 18F-fluorouracil localised more strongly (mean 0.0234% [SE 0.0019] of injected activity per mL tissue at 11 min) in liver than in tumours (0.0032% [0.0004]). There was substantial inhibition, after eniluracil administration, of radiotracer uptake and retention in normal liver (mean area under the time versus radioactivity curve 0.927 [SE 0.086] vs 1.857 [0.169] m2 mL(-1) s) and kidneys (1.096 [0.048] vs 5.043 [0.915] m2 mL(-1) s). There was also an increase in plasma uracil and unmetabolised 18F-fluorouracil and an increase in the radiotracer half-life in tumours (2.3 h to >4.0 h). INTERPRETATION: Two events strongly suggested increased exposure of 18F-fluorouracil and its anabolites in the tumours, consistent with the inactivation of dihydropyrimidine dehydrogenase: a selective decrease in radiotracer exposure in normal liver and kidneys compared with tumours; and an increase in radiotracer half-life in tumours.

Administration, Oral↗
PubMed2000

Increased metalloproteinase activity, oxidant production, and emphysema in surfactant protein D gene-inactivated mice.

Targeted ablation of the surfactant protein D (SP-D) gene caused chronic inflammation, emphysema, and fibrosis in the lungs of SP-D (-/-) mice. Although lung morphology was unperturbed during the first 2 weeks of life, airspace enlargement was observed by 3 weeks and progressed with advancing age. Inflammation consisted of hypertrophic alveolar macrophages and peribronchiolar-perivascular monocytic infiltrates. These abnormalities were associated with increased activity of the matrix metalloproteinases, MMP2 and MMP9, and immunostaining for MMP9 and MMP12 in alveolar macrophages. Hydrogen peroxide production by isolated alveolar macrophages also was increased significantly (10-fold). SP-D plays a critical role in the suppression of alveolar macrophage activation, which may contribute to the pathogenesis of chronic inflammation and emphysema.

Animals↗
PubMed2000

Plasticity in the organization and sequences of human KIR/ILT gene families.

The approximately 1-Mb leukocyte receptor complex at 19q13.4 is a key polymorphic immunoregion containing all of the natural killer-receptor KIR and related ILT genes. When the organization of the leukocyte receptor complex was compared from two haplotypes, the gene content in the KIR region varied dramatically, with framework loci flanking regions of widely variable gene content. The ILT genes were more stable in number except for ILT6, which was present only in one haplotype. Analysis of Alu repeats and comparison of KIR gene sequences, which are over 90% identical, are consistent with a recent origin. KIR genesis was followed by extensive duplication/deletion as well as intergenic sequence exchange, reminiscent of MHC class I genes, which provide KIR ligands.

Alu Elements↗
PubMed2000

Identification of the Drosophila melanogaster homologue of the mammalian signal transducer protein, Vav.

Mammalian Vav signal transducer protein couples tyrosine kinase signals with the activation of the Rho/Rac GTPases, thus leading to cell differentiation and/or proliferation. We have isolated and characterized the DroVav gene, the homologue of hVav in Drosophila melanogaster. DroVav encodes a protein (793 residues) whose similarity with hVav is 47% and with hVav2 and hVav3 is 45%. DroVav preserves the unique, complex structure of hVav proteins, including the 'calponin homology', dbl homology, pleckstrin homology; SH2 and SH3 domains in addition to regions that are acidic rich, proline rich and cysteine rich. DroVav is located on the X chromosome in polytene interval 18A5;18B and is expressed in all stages of development and in all tissues. In mammalian cells, DroVav is tyrosine-phosphorylated in response to epidermal growth factor receptor (EGFR) induction; in vitro, the DroVav SH2 region is associated with tyrosine-phosphorylated EGFR. Thus, DroVav probably plays a pivotal role as a signal transducer protein during fruit fly development.

3T3 Cells↗
PubMed2000

Desipramine binding to noradrenaline reuptake sites in cardiac sympathetic neurons in man in vivo.

Noradrenergic reuptake blockade is a recognised mechanism of antidepressant action, but the extent of the blockade necessary for therapeutic effect is not known and plasma levels do not provide a guide to therapy. We report a method to assess noradrenaline reuptake blockade in vivo in man using [11C]meta-hydroxyephedrine and the multiple organs' coincidences counter. Eight healthy volunteers had two scans, one with tracer alone and one after preloading with desipramine 50-75 mg p.o. In all subjects, there was an increased washout rate of the radioligand from the heart following preloading (t=4.38; P<0.003) as well as a decrease of the area under the [11C]meta-hydroxyephedrine time activity curve (t=7. 4; P=0.001). In one subject who had three doses of desipramine, the increase in washout rate was dose-dependent. In conclusion, [11C]meta-hydroxyephedrine in the multiple organs' coincidences counter gives a valid, low radiation method to assess noradrenergic reuptake blockade in the clinic.

Adrenergic Uptake Inhibitors↗
PubMed2000

Cytokine and free radical responses of alveolar macrophages in vitro to asbestos fibres.

A method for culturing primary rat alveolar macrophages (AMs) for 14 days was used to compare their responses to crocidolite and chrysotile asbestos fibres. Exposure to crocidolite increased production of tumour necrosis factor-alpha (TNF-alpha) and interleukin 1beta (IL-1beta), whereas exposure to chrysotile did not; neither fibre altered the production of interleukin 6 (IL-6). IL-1beta production increased progressively, while TNF-alpha was fully elevated from day 1. Conversely, chrysotile, but not crocidolite, increased production of superoxide anion and nitric oxide (NO) radicals. These differential responses were only observed by extending the culture beyond the usual 1-3 days.

Animals↗
PubMed2000

The obstetrician-gynecologist's role in vaccine-preventable diseases and immunization.

OBJECTIVE: To assess by survey the immunization role currently played obstetrician-gynecologists in the state of Michigan. METHODS: Masked questionnaires requesting demographic, knowledge-based, practice, and attitudinal data were sent to 850 ACOG-registered fellows. RESULTS: Three hundred sixty-five physicians responded, 313 of whom were in active practice. Most were male (70%) and graduated from medical school between 1970 and 1989 (68%). The majority provided both obstetric and gynecologic services. The minority (47%) specifically identified themselves as primary care providers. Only 15% of respondents considered screening for vaccine-preventable diseases to be outside the realm of routine obstetric-gynecologic care. In practice, however, 19% did not screen their obstetric patients for any vaccine-preventable diseases, and only 10% assessed their patients for all nine vaccine-preventable diseases listed in the questionnaire. In gynecologic patients, almost 40% of physicians did not assess for any vaccine-preventable disease. A wide range in knowledge level was identified concerning vaccine-preventable diseases, immunization recommendations, and vaccine safety. CONCLUSION: These data show a discrepancy between perceived responsibilities and actual practice patterns of obstetrician-gynecologists regarding vaccine-preventable diseases and the immunization of women. Limitations in current knowledge and practical concerns specific to vaccine administration contribute to this disparity.

Female↗
PubMed2000

Conducting a systematic review.

In response to the growing volume of health care literature and the variable quality of reported studies, systematic reviews have increasingly been used to guide health care decisions because of their rigorous summary of the research. Systematic reviews utilise planned methods of identifying, appraising, then summarising the results from individual studies. The steps in performing a systematic review include: preparing a detailed research protocol; selecting criteria for inclusion of articles in the review; systematically searching the published and unpublished literature; determining which articles meet the predefined inclusion criteria; critically appraising the quality of the research; extracting outcome data from the research report and statistically combining data, where appropriate, in order to summarise the best available evidence on the topic of interest. These processes are documented in the systematic review report, and can be subject to peer review and critique like other research.

Humans↗
PubMed2000

A comparison of folding techniques in the chemical synthesis of the epidermal growth factor-like domain in neu differentiation factor alpha/beta.

The 52-residue alpha/beta chimera of the epidermal growth factor-like domain in neu differentiation factor (NDFealpha/beta) has been synthesized and folded to form a three disulfide bridge (Cys182-Cys196, Cys190-Cys210, Cys212-Cys221) containing peptide. We investigated two general strategies for the formation of the intramolecular disulfide bridges including, the single-step approach, which used fully deprotected and reduced peptide, and a sequential approach that relied on orthogonal cysteine protection in which specific pairs are excluded from the first oxidation step. Because there are 15 possible disulfide bridge arrangements in a peptide with six cysteines, the one-step approach may not always provide the desired disulfide pairing. Here, we compare the single-step approach with a systematic evaluation of the sequential approach. We employed the acetamidomethyl group to protect each pair of cysteines involved in disulfide bridges, i.e. Cys182 to Cys196, Cys190 to Cys210 and Cys212 to Cys221. This reduced the number of possible disulfide patterns from 15 to three in the first folding step. We compared the efficiencies of folding for each protected pair using RP-HPLC, mapped the disulfide connectivity of the predominant product and then formed the final disulfide from the partially folded intermediate via 12 oxidation. Only the peptide having the Cys182-Cys196 pair blocked with acetamidomethyl forms the desired disulfide isomer (Cys190-Cys210/Cys212-Cys221) as a single homogeneous product. By optimizing both approaches, as well as other steps in the synthesis, we can now rapidly provide large-scale syntheses of NDFealpha/beta and other novel EGF-like peptides.

Amino Acid Sequence↗
PubMed2000

Concomitant administration of vitamin E does not change the side effects of isotretinoin as used in acne vulgaris: a randomized trial.

BACKGROUND: Isotretinoin treatment is frequently associated with reversible, dose-related side effects. Recent studies claimed that combining vitamin E with high-dose isotretinoin ameliorated isotretinoin-induced side effects. OBJECTIVE: The purpose of this double-blind, randomized study was to determine the effects of a fixed dose of vitamin E on the side effects of isotretinoin for treatment-resistant acne vulgaris. METHODS: One hundred forty subjects were randomly assigned to one of two treatment programs with isotretinoin (1 mg/kg) together with either vitamin E (800 IU/day) or a vitamin E placebo for 20 weeks. The incidence, severity, and duration of the side effects (eg, dry eyes, dry lips) were assessed. RESULTS: A fixed 800 IU/day dose of vitamin E did not improve the incidence, severity, or duration of side effects associated with isotretinoin (1 mg/kg per day). CONCLUSION: Vitamin E did not significantly ameliorate retinoid side effects when combined with 1 mg/kg of isotretinoin in the treatment of acne.

Acne Vulgaris↗
PubMed2000

Elderly norms for the Hopkins Verbal Learning Test-Revised.

The present study evaluates the effects of age, education, and gender in a representative sample of older adults and provides normative data for community-dwelling elderly. Age and gender had significant effects on HVLT-R performance. We provide age- and gender-adjusted normative data. Surprisingly, education level did not affect HVLT-R performance, indicating that education-adjusted norms are not necessary for this measure within this age range. We evaluated a subsample of subjects census-matched on age, education, and gender. These subjects did not differ in overall performance from our entire sample. Therefore, the normative data provided in this paper can be considered to be census-comparable for age, education, and gender.

Aged↗