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Biomedical subjects

Julie Wilson

Publications and source records attributed to Julie Wilson.

8 recordsLinked to original sources
PubMed2006

Intravenous continuous infusion of lidocaine for treatment of equine ileus.

OBJECTIVE: To determine if intravenous lidocaine is useful and safe as a treatment for equine ileus. STUDY DESIGN: Prospective double-blinded placebo-controlled trial. STUDY POPULATION: Horses (n = 32) with a diagnosis of postoperative ileus (POI) or enteritis and that had refluxed >20 L or had been refluxing for >24 hours. METHODS: Refluxing horses were administered lidocaine (1.3 mg/kg intravenously [IV] as a bolus followed by a 0.05 mg/kg/min infusion) or saline (0.9% NaCl) solution placebo for 24 hours. Variables evaluated included volume and duration of reflux, time to 1st fecal passage, signs of pain, analgesic use, heart rate and arrhythmias, respiratory rate, temperature, days of hospitalization, outcome (survival to discharge), and complications. RESULTS: Of the lidocaine-treated horses, 65% (11/17) stopped refluxing within 30 hours (mean+/-SD, 15.2+/-2.4 hours) whereas 27% (4/15) of the saline-treated horses stopped within 30 hours. Fecal passage was significantly correlated with response to treatment; horses that responded to lidocaine passed feces within 16 hours of starting the infusion. Compared with placebo treatment, lidocaine treatment resulted in shorter hospitalization time for survivors, equivalent survival to discharge, no clinically significant changes in physical or laboratory variables, and no difference in the rate of incisional infections, jugular thrombosis, laminitis, or diarrhea. Muscle fasciculations occurred in 3 lidocaine-treated horses (18%). CONCLUSION: IV lidocaine significantly improved the clinical course in refluxing horses with minimal side effects. CLINICAL RELEVANCE: At the infusion rate studied, IV lidocaine is safe and should be considered for the treatment of equine ileus.

Abdominal Pain↗
PubMed2005

Benefits of automated crystallization plate tracking, imaging, and analysis.

We describe the design of a database and software for managing and organizing protein crystallization data. We also outline the considerations behind the design of a fast web interface linking protein production data, crystallization images, and automated image analysis. The database and associated interfaces underpin the Oxford Protein Production Facility (OPPF) crystallization laboratory, collecting, in a routine and automatic manner, up to 100,000 images per day. Over 17 million separate images are currently held in this database. We discuss the substantial scientific benefits automated tracking, imaging, and analysis of crystallizations offers to the structural biologist: analysis of the time course of the trial and easy analysis of trials with related crystallization conditions. Features of this system address requirements common to many crystallographic laboratories that are currently setting up (semi-)automated crystallization imaging systems.

Crystallization↗
PubMed2005

Protective cytotoxic T-cell responses induced by venezuelan equine encephalitis virus replicons expressing Ebola virus proteins.

Infection with Ebola virus causes a severe disease accompanied by high mortality rates, and there are no licensed vaccines or therapies available for human use. Filovirus vaccine research efforts still need to determine the roles of humoral and cell-mediated immune responses in protection from Ebola virus infection. Previous studies indicated that exposure to Ebola virus proteins expressed from packaged Venezuelan equine encephalitis virus replicons elicited protective immunity in mice and that antibody-mediated protection could only be demonstrated after vaccination against the glycoprotein. In this study, the murine CD8(+) T-cell responses to six Ebola virus proteins were examined. CD8(+) T cells specific for Ebola virus glycoprotein, nucleoprotein, and viral proteins (VP24, VP30, VP35, and VP40) were identified by intracellular cytokine assays using splenocytes from vaccinated mice. The cells were expanded by restimulation with peptides and demonstrated cytolytic activity. Adoptive transfer of the CD8(+) cytotoxic T cells protected filovirus naïve mice from challenge with Ebola virus. These data support a role for CD8(+) cytotoxic T cells as part of a protective mechanism induced by vaccination against six Ebola virus proteins and provide additional evidence that cytotoxic T-cell responses can contribute to protection from filovirus infections.

Amino Acid Sequence↗
PubMed2005

Image storage for automated crystallization imaging systems.

To use crystallography for the determination of the three-dimensional structures of proteins, protein crystals need to be grown. Automated imaging systems are increasingly being used to monitor these crystallization experiments. These present problems of accessibility to the data, repeatability of any image analysis performed and the amount of storage required. Various image formats and techniques can be combined to provide effective solutions to high volume processing problems such as these, however lack of widespread support for the most effective algorithms, such as JPeg2000 which yielded a 64% improvement in file size over the bitmap, currently inhibits the immediate take up of this approach.

Algorithms↗
PubMed2004

Cloning of oestrogen receptor beta from Old and New World primates: identification of splice variants and functional analysis.

Oestrogens have a major impact on reproductive function in both males and females. Two oestrogen receptor genes known as ERalpha (ESR1NR3A1) and ERbeta (ESR2NR3A2) have been cloned. Splice variant isoforms of the ERbeta gene have been identified in human, bovine and rodents and it has been suggested that the existence of these forms can influence oestrogen responsiveness. In the human, splicing of an alternative eighth exon results in the formation of a C-terminal variant called hERbetacx, or hERbeta2, but this isoform has not been identified in other species. The aim of the present study was to clone ERbeta cDNAs from primates so as to determine how closely they resembled the ERbeta isoforms found in the human. The two species studied were the stump-tailed macaque (Macaca arctoides), an Old World primate, and the common marmoset (Callithrix jacchus jacchus), a New World primate. Full length ERbeta (wild type, ERbeta1) cDNAs were cloned from macaque and marmoset; they encoded proteins of similar size to those found in human (59 and 54 kDa, long and short forms respectively) and shared significant sequence homology (97.5% in macaque and 93.8% in marmoset) with the human peptide sequence. Full length cDNAs homologous to the hERbeta2 variant were identified in both primates. Marmoset ERbeta2 was slightly shorter than that of human ERbeta2 (54 kDa compared with 55 kDa) and did not contain the peptide sequence used to raise an anti-hERbeta2 antibody. All the macaque ERbeta2 cDNAs contained 56 bp of intronic sequence which included an in-frame stop codon resulting in translation of a truncated protein ( approximately 35 kDa). In all three species, truncated, alternatively spliced mRNAs lacking exon 5 were isolated on multiple occasions from all tissue extracts. In transient transfection assays, ERbeta2-containing constructs were unable to induce transcription of an oestrogen response element (ERE) reporter plasmid in the presence of oestradiol. ERbeta1 from human, macaque and marmoset exhibited minor differences in their ability to induce transcription of the ERE reporter when incubated with different ligands (oestradiol, PPT, DPN, 5-alpha-androstane-3-beta, 17beta-diol (3betaAdiol), genistein) and this may be due to amino acid substitutions within their ligand binding domains. In conclusion, we have identified and cloned wild type ERbeta (ERbeta1) from macaque and marmoset and demonstrated that splice variant mRNAs homologous to hERbeta2 are formed in both species. The marmoset monkey, therefore, provides a suitable animal model in which to investigate the impact of ERbeta variant expression on tissue responsiveness to oestrogens.

Alternative Splicing↗
PubMed2003

Design, synthesis and biological activity of novel dimethyl-[2-[6-substituted-indol-1-yl]-ethyl]-amine as potent, selective, and orally-bioavailable 5-HT(1D) agonists.

A novel series of highly potent human 5-HT(1D) agonists, dimethyl-[2-[6-substituted-indol-1-yl]-ethyl]-amine, was synthesized. Structure-activity relationship (SAR) investigation revealed 4-[1-(2-dimethylamino-ethyl)-1H-indol-6-yl]-tetrahydro-thiopyran-4-ol, 11b (ALX-2732), as a potent (K(i)=2.4 nM) agonist at the human 5-HT(1D) receptor with good selectivity over the other serotonin receptor subtypes. This compound demonstrated favorable in vitro metabolic stability in human and rat liver microsomes and was found to be orally bioavailable in rats (F(po)=51%).

Administration, Oral↗
PubMed2002

Towards the automated evaluation of crystallization trials.

A method to evaluate images from crystallization experiments is described. Image discontinuities are used to determine boundaries of artifacts in the images and these are then considered as individual objects. This allows the edge of the drop to be identified and any objects outside this ignored. Each object is evaluated in terms of a number of attributes related to its size and shape, the curvature of the boundary and the variance in intensity, as well as obvious crystal-like characteristics such as straight sections of the boundary and straight lines of constant intensity within the object. With each object in the image assigned to one of a number of different classes, an overall report can be given. The objects to be considered have no predefined shape or size and, although one may expect to see straight edges and angles in a crystal, this is not a prerequisite for diffraction. This means there is much overlap in the values of the variables expected for the different classes. However, each attribute gives some information about the object in question and, although no single attribute can be expected to correctly classify an image, it has been found that a combination of classifiers gives very good results.

Algorithms↗