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Biomedical subjects

A G Kelly

Publications and source records attributed to A G Kelly.

9 recordsLinked to original sources

Rent1, a trans-effector of nonsense-mediated mRNA decay, is essential for mammalian embryonic viability.

The ability to detect and degrade transcripts that lack full coding potential is ubiquitous but non-essential in lower eukaryotes, leaving in question the evolutionary basis for complete maintenance of this function. One hypothesis holds that nonsense-mediated RNA decay (NMD) protects the organism by preventing the translation of truncated peptides with dominant negative or deleterious gain-of-function potential. All organisms studied to date that are competent for NMD express a structural homolog of Saccharomyces cerevisiae Upf1p. We have now explored the consequences of loss of NMD function in vertebrates through targeted disruption of the Rent1 gene in murine embryonic stem cells which encodes a mammalian ortholog of Upf1p. Mice heterozygous for the targeted allele showed no apparent phenotypic abnormalities but homozygosity was never observed, demonstrating that Rent1 is essential for embryonic viability. Homozygous targeted embryos show complete loss of NMD and are viable in the pre-implantation period, but resorb shortly after implantation. Furthermore, Rent1(-/-) blastocysts isolated at 3.5 days post-coitum undergo apoptosis in culture following a brief phase of cellular expansion. These data suggest that NMD is essential for mammalian cellular viability and support a critical role for the pathway in the regulated expression of selected physiologic transcripts.

Animals↗

Osteogenic sarcoma and phthisis bulbi: a case report.

PURPOSE: To describe a case of osteogenic sarcoma (osteosarcoma) that developed within a phthisical eye. METHOD: Case report. RESULTS: An 86-year-old woman with a 20-year history of phthisis bulbi developed pain and proptosis. Tumor was identified by computed tomography. An exenteration was performed, and osteogenic sarcoma was identified. CONCLUSION: Osteogenic sarcoma is the most common primary malignant tumor of bone. In the orbit it frequently is associated with prior irradiation for retinoblastoma. We describe the first case of osteogenic sarcoma that developed de novo from bone within a phthisical eye.

Aged↗

Disappointing results following resurfacing of facial skin with CO2 lasers for prophylaxis of keratoses and cancers.

BACKGROUND: With the development of the short-pulse CO2 laser it was hoped that this resurfacing would prevent recurrent actinic keratoses and basal cell cancers similar to resurfacing with dermabrasion, laser abrasion, and deep chemical peel. However, we have begun to see patients that are developing keratoses and cancers within months following laser resurfacing. OBJECTIVE: To document the problems of recurrent keratoses and basal cell cancers in patients following CO2 laser resurfacing. METHODS: Thirty-five patients with extreme sun damage were seen at 3, 6, and 12 months following CO2 laser resurfacing for repeat color and ultraviolet photography and clinical examination to look for erythematous dyskeratotic lesions or papules with pearly borders. RESULTS: Five of our patients (14.3%) who had undergone recent CO2 resurfacing developed actinic keratoses and basal cell cancers. CONCLUSION: CO2 laser resurfacing is not as effective as dermabrasion, chemabrasion, and deep chemical peel for the prophylaxis of actinic keratoses and basal cell cancers, especially in Fitzpatrick type I and II patients.

Adult↗

Troubleshooting in gene splicing by overlap extension: a step-wise method.

A step-wise method for cloning intron-containing genes from genomic DNA is described. The two exons of the human proinsulin gene were separately amplified in two steps using, in the first step, completely homologous primers. This reduces unwanted interactions between mismatched primers and a complex DNA template such as genomic DNA. The fragments were amplified in a second step polymerase chain reaction (PCR) using mismatched primers that incorporated additional bases complementary to the other exon, and these products were spliced together in a third step PCR.

Cloning, Molecular↗

Accumulation and persistence of chlorobiphenyls, organochlorine pesticides and faecal sterols at the Garroch Head sewage sludge disposal site, Firth of Clyde.

The sediment concentrations of organic carbon, faecal sterols, individual chlorobiphenyl congeners and organochlorine pesticides have been measured in seabed cores from the sewage sludge disposal area at Garroch Head in the Firth of Clyde. The measurements confirm the accumulative nature of the site with high levels of sedimentary faecal sterols (152 mg kg(-1) coprostanol). Levels of chlorobiphenyls, DDT compounds and dieldrin in surface sediment were elevated by factors of 12, 40 and 120, respectively, over those observed at a site remote from the effects of dumping. Total chlorobiphenyl levels of 515 microg kg(-1) Arochlor 1254 in surface sediment were comparable to levels found in other areas heavily contaminated with sewage sludge. The 20-cm depth of heavily sludge-contaminated sediment overlays a mixed sludge/basal sediment layer some 10 cm in depth. Levels of organochlorine contaminants were elevated to depths of 90 cm in the sediment, suggesting that the surface layer is a source of contaminants to the deeper sediment. Within the upper 15-20 cm sediment in the disposal area, chlorobiphenyls are conservative, the variation in their concentration with respect to depth being related to historical input. Lindane and possibly dieldrin, and hexachlorobenzene are not conservative. Faecal sterols are removed in sub-surface sediment, in contrast to conservative behaviour previously found at other sewage polluted sites.

Journal Article↗