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Biomedical subjects

T Jones

Publications and source records attributed to T Jones.

At least 109 records · Page 6Linked to original sources
PubMed1999

A novel gene (PLU-1) containing highly conserved putative DNA/chromatin binding motifs is specifically up-regulated in breast cancer.

A novel human gene (PLU-1) has been identified which shows a highly restricted expression in normal adult tissues but which is consistently expressed in breast cancers. A fragment of the PLU-1 cDNA was identified by differentially screening a fetal brain library with cDNAs prepared from ce-1 cells (a human mammary epithelial cell line overexpressing c-ErbB2) treated or untreated with the antibody 4D5, which inhibits c-ErbB2 phosphorylation. Clones covering the full cDNA sequence of 6.4 kilobases were isolated from a breast cancer cDNA library. Although expression of PLU-1 in ce-1 cells is regulated by signaling from c-ErbB2, the gene is expressed in all the breast cancer cell lines examined, in cells cultured from primary breast cancers, and in the invasive and in situ components of primary breast cancers. Translation of the open reading frame predicts a protein of 1544 amino acids, which contains three PHD/LAP motifs, a specific DNA-binding domain found in a Drosophila protein (dri) and novel domains showing extensive homology with other human and non human gene products. Transient transfection of cell lines with MYC-tagged PLU-1 showed the protein to be localized in the nucleus and associated with discrete foci. The presence of the dri motif and PHD/LAP fingers together with the clear nuclear localization and consistent expression in breast cancers, suggest a role for PLU-1 in regulating gene expression in breast cancers.

Amino Acid Sequence↗
PubMed1999

An automated radiosynthesis of 2-[11C]thymidine using anhydrous [11C]urea derived from [11C]phosgene.

2-[11C]Thymidine has been produced from [11C]methane via [11C]phosgene and [11C]urea. Anhydrous [11C]urea was prepared from [11C]phosgene by reaction with liquid ammonia. This novel approach avoids the problems associated with the synthesis of anhydrous [11C]urea from [11C]cyanide. A fully automated system based on a modular approach and under PLC control has been developed. The system provides 2-[11C]thymidine reliably and reproducibly for clinical PET studies. The radiosynthesis takes 45-50 min from [11C]methane and the average yield was 1.5-3.3 GBq (40-90 mCi). The specific radioactivity was typically in the range 29.6-51.8 GBq mumol-1 (0.8-1.4 Ci mumol-1) at EOS corresponding to 6-12 micrograms of stable thymidine. The radiochemical yield of 2-[11C]thymidine was ca. 14% from [11C]methane.

Carbon Radioisotopes↗
PubMed1999

Cowpox: reservoir hosts and geographic range.

It is generally accepted that the reservoir hosts of cowpox virus are wild rodents, although direct evidence for this is lacking for much of the virus's geographic range. Here, through a combination of serology and PCR, we demonstrate conclusively that the main hosts in Great Britain are bank voles, wood mice and short-tailed field voles. However, we also suggest that wood mice may not be able to maintain infection alone, explaining the absence of cowpox from Ireland where voles are generally not found. Infection in wild rodents varies seasonally, and this variation probably underlies the marked seasonal incidence of infection in accidental hosts such as humans and domestic cats.

Animals↗
PubMed1999

Cholera toxin-induced alteration of the phenotype and behaviour of an ovarian carcinoma cell line, SR8.

Cholera toxin (CT) has been reported to cause a variety of effects on several different cell types. Recently, CT has been shown to increase the susceptibility of ovarian carcinoma cells to cytotoxicity mediated by a variety of effector cells (natural killer, lymphokine-activated killer cells and tumour-associated lymphocytes derived from ascites of ovarian cancer patients) of both autologous and allogenic background. In the present study, CT demonstrated several effects on a newly established ovarian carcinoma line (SR8)1 when added to the culture medium at a concentration of 12.5 ng/mL for 2 days. Cholera toxin altered SR8 morphology to a uniform polygonal cellular shape, with less cell dispersion than the non-CT treated cells. Cholera toxin prolonged the population doubling time by approximately 10 h. The CT-treated SR8 cells exhibited reduced epidermal growth factor receptor expression (39 versus 50%), and increased carbohydrate antigen 125 expression (45 versus 2%) in both immunocytochemical and quantitative flow cytometric analyses. These changes in morphology and tumour marker expression were reversible when CT was removed from the culture. The CT-treated SR8 cells showed reduced capacity to generate tumours in female nude mice in comparison with non-CT treated cells, which produce both subcutaneous and intraperitoneal xenografts with local invasion in an animal model. Cytogenetic analysis of the cell line SR8 before and during treatment with CT showed no new clonal rearrangements. The possible mechanisms involved and the influence of CT on the biological behaviour of ovarian tumour cells are discussed.

Animals↗
PubMed1999

The human dendritic cell marker CD83 maps to chromosome 6p23.

The chromosomal localization of the human CD83 gene was determined using somatic cell hybrids, a radiation hybrid mapping panel and FISH analysis on human metaphase chromosomes. PCR-based analysis of a single chromosome hybrid panel identified the presence of the CD83 gene on human chromosome 6 and subsequent analysis of the Genebridge4 radiation panel located the gene between AFMa192wg9 and AFMb322wd1 with a lod score of 9.2. Finally, using FISH analysis the CD83 gene was localized to chromosome 6 band p23.

Antigens, CD↗
PubMed1999

Measurement of changes in opioid receptor binding in vivo during trigeminal neuralgic pain using [11C] diprenorphine and positron emission tomography.

The binding of [11C]diprenorphine to mu, kappa, and delta subsites in cortical and subcortical structures was measured by positron emission tomography in vivo in six patients before and after surgical relief of trigeminal neuralgia pain. The volume of distribution of [11C]diprenorphine binding was significantly increased after thermocoagulation of the relevant trigeminal division in the following areas: prefrontal, insular, perigenual, mid-cingulate and inferior parietal cortices, basal ganglia, and thalamus bilaterally. In addition to the pain relief associated with the surgical procedure, there also was an improvement in anxiety and depression scores. In the context of other studies, these changes in binding most likely resulted from the change in the pain state. The results suggest an increased occupancy by endogenous opioid peptides during trigeminal pain but cannot exclude coexistent down-regulation of binding sites.

Aged↗
PubMed1999

Comparison of sensitivity of immunofluorescent microscopy to that of a combination of immunofluorescent microscopy and immunomagnetic separation for detection of Cryptosporidium parvum oocysts in adult bovine feces.

A direct immunofluorescence assay (DFA) (Merifluor; Meridian Diagnostics, Inc., Cincinnati, Ohio) was compared to an immunomagnetic separation (IMS) assay (Dynabeads; Dynal, Inc., Lake Success, N.Y.) coupled with immunofluorescent microscopy (Waterborne, Inc., New Orleans, La.) for their ability to detect low concentrations of Cryptosporidium parvum oocysts in adult bovine fecal material. IMS-DFA resulted in a 2-log-unit increase in sensitivity (10 oocysts/g) compared to DFA alone (1,000 oocysts/g). The higher sensitivity obtained with IMS-DFA resulted from testing 2 g of fecal material instead of the 13 to 19 mg of fecal material tested in the DFA; the increased sensitivity was not attributable to a higher percent recovery.

Animals↗
PubMed1999

Isolation and properties of the complex between the enhancer binding protein NIFA and the sensor NIFL.

In Azotobacter vinelandii, activation of nif gene expression by the transcriptional regulatory enhancer binding protein NIFA is controlled by the sensor protein NIFL in response to changes in levels of oxygen and fixed nitrogen in vivo. NIFL is a novel redox-sensing flavoprotein which is also responsive to adenosine nucleotides in vitro. Inhibition of NIFA activity by NIFL requires stoichiometric amounts of the two proteins, implying that the mechanism of inhibition is by direct protein-protein interaction rather than by catalytic modification of the NIFA protein. The formation of the inhibitory complex between NIFL and NIFA may be regulated by the intracellular ATP/ADP ratio. We show that adenosine nucleotides promote complex formation between purified NIFA and NIFL in vitro, allowing isolation of the NIFL-NIFA complex. The complex can also be isolated from cell extracts containing coexpressed NIFL and NIFA in the presence of MgADP. Removal of the nucleotide causes dissociation of the complex. Experiments with truncated proteins demonstrate that the amino-terminal domain of NIFA and the C-terminal region of NIFL potentiate the ADP-dependent stimulation of NIFL-NIFA complex formation.

Adenosine Diphosphate↗
PubMed1999

A colorectal cell line with alterations in E-cadherin and epithelial biology may be an in vitro model of colitis.

BACKGROUND: It has been shown previously in ulcerative colitis tissue that E-cadherin can occasionally be mutated in the extracellular domain early in neoplastic progression. E-cadherin is known to maintain differentiation and inhibits invasion in vivo. AIMS: To assess the mechanisms by which such dysfunction occurs. METHODS: Four human colorectal cancer cell lines, HCA-7 colonies 1, 3, 6, and 30, derived from a single heterogeneous colorectal cancer were studied. The HCA-7 cell line has p53 mutations and a random errors of replication "positive" phenotype, as is seen in early colitis associated cancers or hereditary nonpolyposis coli cancer (HNPCC). RESULTS: Cell lines 6 and 30 expressed E-cadherin abundantly and this correlated positively with their degree of differentiation and organisation; however, both cell lines had loss of heterozygosity of E-cadherin. Interestingly, E-cadherin production was downregulated in the poorly differentiated cell line 1, and this was associated with major chromosomal rearrangements of 16q. This cell line also had a mutation in the homophilic binding domain of exon 4, which was associated with disaggregation by low titres of a function blocking antibody, and an invasive phenotype. CONCLUSIONS: These multiple biological alterations further characterise the complex association that E-cadherin has with tumour heterogeneity and suggest that this series of cell lines may be a useful model of colitis associated or HNPCC associated tumorigenesis.

Agar↗
PubMed1999

Present and future capabilities of molecular imaging techniques to understand brain function.

This article focuses on the use of positron emitting tracers and positron emission tomography (PET) as the most specific and sensitive means for imaging molecular interactions and pathways within the human brain. The concept of the imaging science of PET is developed whereby the key components that contribute to the overall accuracy of the image of molecular activity need to be separately optimized. These include radiolabelling of tracer molecules and ligands with radioisotopes of short radioactive half-life, the search for specific radioligands and tracers, and hence the need to mine molecular databases for molecules suitable for in-vivo imaging. The sensitivity and accuracy of PET scanners need to be advanced along with improvements in the signal-to-noise ratio of the tomographic reconstruction algorithms. Finally, the models used for the analysis of serial time frames of kinetic data need to be developed, the operation of which have to be effected with the minimum of noise propagation. The future use of PET for drug discovery and development is discussed whereby it offers proof principle for assays of in-vivo expression of therapeutic molecular targets as accessed from the blood stream; tissue pharmacokinetics of novel compounds; degree of occupancy of molecular targets; and pharmacodynamic measures of drug action. The future application of PET rests heavily on drug discoverers contributing to discovering specific PET radioligands and tracers in order to provide these assays through in-vivo molecular imaging.

Algorithms↗
PubMed1999

Radio-imaging in small animals.

As the resolution of radio-imaging systems improves, the prospect of in-vivo imaging of small animals becomes more attractive. Purpose-built positron emission tomography (PET) scanners capable of imaging individual tissues within the rat brain are now in routine experimental use and in-vivo tracer and saturation-kinetic studies are now possible. The study of small animals in this way does have intrinsic problems and constraints associated with it. For example, the animal must be completely immobilized, stable ligand within the radiolabelled preparation may be limiting and anatomical definition may be poor. In spite of this, consistent, semi-quantitative data can be produced and in-vivo radio-imaging can provide a genuine and unique complement to more conventional techniques. Animal numbers can be significantly reduced and the quality of data improved due to reduced inter-animal variation, and longitudinal studies, to monitor disease progression, are feasible. As the resolution of imaging systems improves still further, such studies could be extended to mouse, in addition to rat, models of disease.

Animals↗
PubMed1999

Tumor, normal tissue, and plasma pharmacokinetic studies of fluorouracil biomodulation with N-phosphonacetyl-L-aspartate, folinic acid, and interferon alfa.

PURPOSE: To evaluate the effect of N-phosphonacetyl-L-aspartate (PALA), folinic acid (FA), and interferon alfa (IFN-alpha) biomodulation on plasma fluorouracil (5FU) pharmacokinetics and tumor and liver radioactivity uptake and retention after [18F]-fluorouracil (5-[18F]-FU) administration. PATIENTS AND METHODS: Twenty-one paired pharmacokinetic studies were completed on patients with colorectal, gastric, and hepatocellular cancer, utilizing positron emission tomography (PET), which allowed the acquisition of tumor, normal tissue, and plasma pharmacokinetic data and tumor blood flow (TBF) measurements. The first PET study was completed when the patient was biomodulator-naive and was repeated on day 8 after the patient had been treated with either PALA, FA, or IFN-alpha in recognized schedules. RESULTS: TBF was an important determinant of tumor radioactivity uptake (r = .90; P < .001) and retention (r = .96; P < .001), for which radioactivity represents a composite signal of 5-[18F]-FU and [18F]-labeled metabolites and catabolites. After treatment with PALA, TBF decreased (four of four patients; P = .043), as did tumor radioactivity exposure (five of five patients; P = .0437), with no change in plasma 5FU clearance. With FA treatment, there were no differences observed in whole-body metabolism, plasma 5FU clearance, or tumor and liver pharmacokinetics. IFN-alpha had measurable effects on TBF and 5-[18F]-FU metabolism but had no apparent affect on liver blood flow. CONCLUSION: The administration of PALA and IFN-alpha produced measurable changes in plasma, tumor, and liver pharmacokinetics after 5-[18F]-FU administration. No changes were observed after FA administration. In vivo effects may negate the anticipated therapeutic advantage of 5FU biomodulation with some agents.

Adult↗
PubMed1999

Identification of inadequately cleaned equipment used in a sheep carcass-breaking process.

Aeromonads deposited on pork during a carcass-breaking process were recovered on hydrophobic grid membrane filters placed on ampicillin-dextrin-ethanol agar. Isolates from 85 honey-yellow colonies from filters on that medium were Aeromonas hydrophila (95%) or Vibrio sp. (5%). Presumptive aeromonads, coliforms, and Escherichia coli in swab samples from product passing through a sheep carcass-breaking process were enumerated by hydrophobic grid membrane filtration techniques with a detection level of 1 CFU/100 cm2. Total aerobic counts were determined by a spread plate procedure with a detection level of 1 CFU/cm2 The numbers of aerobes, coliforms, and E. coli in the product were apparently unaffected by the carcass-breaking process, although coliforms and E. coli appeared to be redistributed from shoulder to loin and leg portions. However, the numbers of aeromonads on product increased by about two orders of magnitude as a result of the process. Few bacteria were recovered from most cleaned, large items of equipment, but aerobes, coliforms, and aeromonads were recovered at log total numbers of 5.25, 3.96, and 3.26, respectively, from most of 25 samples from bars supporting a conveyor belt. Also, aerobes, coliforms, E. coli, and aeromonads were recovered from 25 supposedly cleaned steel mesh gloves at log total numbers of 10.14, 5.54, 4.73, and 8.30, respectively. Those findings indicate that inspection of cleaned equipment and microbiological sampling of only food-contacting surfaces, as is the current practice at meat plants, cannot provide assurance that the cleaning of carcass-breaking equipment is adequate. Instead, enumeration of indicator organisms on product passing through a process seems to be required as well, with subsequent sampling of equipment to identify sources of contaminants if increases in numbers during processing are observed. For surety of adequate cleaning, enumeration of several types of indicator organism may be necessary, as increases during processing in the numbers of organisms that are present in relatively large numbers on product entering a process may be difficult to detect.

Aeromonas↗
PubMed1999

Assessment of the microbiological conditions of tails, tongues, and head meats at two beef-packing plants.

Newly skinned tails of beef carcasses at two packing plants were similarly contaminated with total aerobes and with coliforms that were largely Escherichia coli at log mean numbers about 3.5/cm2 and 4.5/100 cm2, respectively. The log mean numbers of aerobes and coliforms on the skinned tails after washing at plant A were, respectively, 1 and 2 log units less than the numbers on the newly skinned tails. At plant B, the log mean numbers of aerobes on skinned and on washed tails were similar while the log mean numbers of E. coli on washed tails were only about 1 log unit less than the numbers on skinned tails. Cooling of tails on racks in a chiller at plant B reduced the log mean numbers of E. coli by about 1 log unit but did not reduce the numbers of total aerobes. Tongues in the heads of carcasses at both plants were similarly contaminated with total aerobes and with coliforms that were largely E. coli at log mean numbers of about 4.5/cm2 and 4.5/100 cm2, respectively. The log mean numbers of aerobes on and the log total number of E. coli recovered from washed tongues were, respectively, about 2 and 4 log units less than for unwashed tongues at plant A and about 1 and 3 log units less than for unwashed tongues at plant B. The log mean numbers of aerobes and E. coli on washed cheeks and lips were both about 2 log units less than the numbers on unwashed tongues at both plants. With appropriate collection and washing procedures, the microbiological conditions of beef tails, tongues, and head meats can apparently be comparable to those of primal cuts and manufacturing beef at the times that the products are packed.

Animals↗
PubMed1999

Where do we go from here? Future directions for positive health outcomes.

The history of nursing and its perspective on the individual as a part of a family and community, nursing's basic professional preparation as generalists, the advanced preparation of Nurse Practitioners, and direct access to clients position the NP to be the premier professional in health promotion. Suggestions for action in education and in practice offer methods for acquiring the recognition of this professional competence as a hallmark of the primary care Nurse Practitioner.

Forecasting↗