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Biomedical subjects

Leslie Mitchell

Publications and source records attributed to Leslie Mitchell.

4 recordsLinked to original sources

Persistent respiratory symptom can be a manifestation of neurofibromatosis-1.

A 3-year old boy with neurofibromatosis-1 presented with persistent respiratory symptoms and X-ray changes. High resolution computerised tomography (CT), bronchoscopy and spiral CT showed a mediastinal mass encasing and compressing the left main stem bronchus. Surgical removal and histology of the mass revealed a neurofibroma. Repeat scan six months post-surgery showed some persistence of the mass. Symptomatic, mediastinal neurofibroma in the paediatric age group is very rare. We could not find any previous report of a neurofibroma encasing the mediastinal structures. This case also demonstrates that persistent respiratory symptom in a patient with neurofibromatosis-1 warrants a search for intra-thoracic neurofibroma.

Humans↗

Liver-targeted gene therapy by SV40-based vectors using the hydrodynamic injection method.

Efficient reconstitution of defective genes in hepatocytes could be used to treat various liver and systemic diseases through gene therapy. To explore the potential of SV40-based vectors in liver gene therapy, we constructed SV/luc, an SV40 T-antigen replacement transduction vector, that was propagated on COS and COT cells, which supply the SV40 T-antigen in trans. For liver targeting, BALB/C mice were injected via the tail vein with SV/luc stocks containing 3 x 10(6) to 10(8) transducing units in a volume of 1-2 ml. Luciferase activity was monitored with a light-detection cooled charged-coupled device (CCCD) camera, which enables continuous in vivo measurement of luc expression. The SV40 vector proved to be efficient in gene delivery to the liver, leading to long-term (> or =107 days) transgene expression in hepatocytes. Optimal results were obtained with 3 x 10(6) to 3 x 10(7) transducing units. The hydrodynamic vector delivery method caused transient liver inflammatory changes, with full recovery within days. Low levels of SV40-neutralizing antibodies were detected in the sera of treated mice; however, there was no indication of vector or transgene-specific cellular immune responses. Vectors packaged in vitro, using recombinant capsid proteins and plasmid DNA, were also effective in liver transduction. These results suggest that SV40 vectors may be useful for liver gene therapy.

Alanine Transaminase↗

First report of no-react bovine internal mammary artery performance and patency.

BACKGROUND: No-React treatment is known to render tissues resistant to calcific degeneration and to reduce early inflammatory response. No-React bovine internal mammary artery (NR-IMA) is available for restricted use in Europe. In this first study, our aim was to use magnetic resonance imaging (MRI) to investigate the clinical performance and patency rates of this conduit. METHODS: Seven patients received 8 grafts with NR-IMA. Approval from the Medical Devices Agency of the United Kingdom was obtained for use of this material. One patient needed salvage coronary artery bypass grafting (CABG). Graft patency was investigated with cardiac MRI. One patient was excluded from the MRI study because of the presence of intracerebral metal clips. The mean follow-up period was 2.5 years with a range of 1 to 4.5 years. RESULTS: There was no mortality in this group. After treatment 6 patients were asymptomatic, and 1 patient had class II anginal symptoms. Four (57%) of the 7 NR-IMA grafts remained patent. The longest patency was 4.5 years in a patient who underwent salvage CABG. Other associated grafts in this cohort of patients were 5 left internal mammary arteries (all patent), 1 radial artery graft (patent), and 7 saphenous vein grafts (4 [57%] of 7 patent). There were no occluded NR-IMA grafts in a patient with patent vein grafts. CONCLUSION: We concluded that at 2.5 year follow-up, NR-IMA had a patency rate of 57% (4 of 7 cases). This rate matched the vein graft patency rate in this cohort of patients. With the longest patency of 4.5 years, use of NR-IMA seems to hold promise for the future.

Aged↗

Molecular cloning and characterization of rainbow trout (Oncorhynchus mykiss) CCAAT/enhancer binding protein beta.

A full-length cDNA encoding CCAAT/enhancer-binding protein beta (C/EBPbeta) was cloned from rainbow trout by anchored PCR. The putative 291 amino acid protein has 53% and 32% identity to the zebrafish and Japanese flounder sequences, respectively, and 30-34% identity to tetrapod homologues. This clone contains most conserved C/EBPbeta domains except the second transactivation domain just like the zebrafish homologue. Also similar to zebrafish, rainbow trout produces only shorter C/EBPbeta isoforms (LAP and LIP) but not the longer isoform (LAP*). However, unlike the zebrafish and Japanese flounder homologues, trout C/EBPbeta has the short open reading frame (uORF) upstream of the start codon for LAP but in an alternate reading frame, a feature of tetrapod C/EBPbeta genes. In normal rainbow trout, C/EBPbeta mRNA was detected in peripheral blood leukocytes, head kidney, posterior kidney, liver, spleen, gills, intestine and muscle. RT-PCR revealed that transcript levels of trout C/EBPbeta are clearly higher in sodium alginate-induced peritoneal cells than in head kidney and peritoneal cells of saline-injected fish or head kidney cells of alginate-injected fish. Together with expression in immunologically important tissues, this indicates that C/EBPbeta is likely to be involved in the immune response just as in mammals. Southern hybridization suggested that C/EBPbeta is a single copy gene. There are no introns in this C/EBPbeta gene, just like the mammalian homologues. These data suggest that we have obtained the trout ortholog of C/EBPbeta.

Amino Acid Sequence↗