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Biomedical subjects

Sarah J Jones

Publications and source records attributed to Sarah J Jones.

4 recordsLinked to original sources

Injuries in homes with certain built forms.

BACKGROUND: Rates of injuries may occur more frequently in different types of homes. METHODS: Retrospective population-based cohort study utilizing three linked databases: a population register, an architectural assessment of homes in the area, and an emergency department-based injury surveillance system. RESULTS: Over 58,000 homes were classified into 94 different types according to age, size, and built form. Among the 112,248 inhabitants, there were 18,044 emergency department attendances for treatment of an injury suffered in the home. Adjusted odds ratio of injuries for residents of purpose-built apartments was substantially elevated for all injuries (2.07; 95% confidence interval [CI]=1.87-2.30) and poisoning episodes (5.6; 95% CI=3.8-8.3). CONCLUSIONS: Residents of apartment buildings have substantially higher injury rates. Additional research is required to investigate the contribution of environmental hazards and behavioral factors underlying these high rates.

Accidents, Home↗

The expression of migration stimulating factor, a potent oncofetal cytokine, is uniquely controlled by 3'-untranslated region-dependent nuclear sequestration of its precursor messenger RNA.

Migration stimulating factor (MSF) is a truncated oncofetal fibronectin isoform expressed by fetal and tumor-associated cells. MSF mRNA is distinguished from other fibronectin isoforms by its size (2.1 kb) and the inclusion of a specific intronic sequence at its 3' end. Initial Northern blot analysis with a MSF-specific probe indicated the presence of this 2.1-kb transcript and an additional unexpected 5.9-kb RNA present in both MSF-secreting (fetal) and nonsecreting (adult) fibroblasts. Our investigations into the nature of these transcripts and their relationship to MSF protein secretion revealed that the 5.9-kb mRNA is a second MSF-encoding transcript. Both these mRNAs have identical coding sequence and differ only in the length of their intron-derived 3'-untranslated region (UTR). The 5.9-kb MSF mRNA is retained in the nucleus whereas the 2.1-kb mRNA is not. MSF-secreting fetal fibroblasts have significantly lower nuclear levels of the 5.9-kb mRNA and correspondingly higher cytoplasmic levels of the 2.1-kb transcript than their nonsecreting adult counterparts. Adult fibroblasts induced to secrete MSF by treatment with transforming growth factor-beta1 displayed similar changes in their respective levels of MSF mRNA, but not those of a control gene. When cloned downstream of a reporter gene, only the longer 3'-UTR retained coding sequence within the nucleus. We conclude that expression of MSF protein is regulated by 3'-UTR truncation of the 5.9-kb nuclear-sequestered "precursor" MSF mRNA and nuclear export of mature 2.1-kb message. Inducible 3'-UTR processing represents a novel regulatory mechanism involved in cancer pathogenesis that may open new avenues for therapeutic gene delivery.

3' Untranslated Regions↗

Home injuries and built form--methodological issues and developments in database linkage.

BACKGROUND: The aim of this body of research is to determine whether injuries in the home are more common in particular types of housing. Previous home injuries research has tended to focus on behaviours or the provision of safety equipment to families with young children. There has been little consideration of the physical environment. This study reports methodological developments in database linkage and analysis to improve researchers abilities to utilise large administrative and clinical databases to carry out health and health services research. METHODS: The study involved linking a database of home injuries obtained from an emergency department surveillance system with an external survey of all homes in an area and population denominators for home types derived from a health service administrative database. Analysis of injury incidence by housing type was adjusted for potential biases due to deprivation and distance to hospital. For non-injured individuals data confidentiality considerations required the deprivation and distance measures be imputed. The process of randomly imputing these variables and the testing of the validity of this approach is detailed. RESULTS: There were 14,081 first injuries in 112,248 residents living in 54,081 homes over a two-year period. The imputation method worked well with imputed and observed measures in the injured group being very similar. Re-randomisation and a repeated analysis gave identical results to the first analysis. One particular housing type had a substantially elevated odds ratio for injury occurrence, OR = 2.07 (95% CI: 1.87 to 2.30). CONCLUSIONS: The method of data linkage, imputation and statistical analysis used provides a basis for improved analysis of database linkage studies.

Accidents, Home↗

Migration-stimulating factor: a genetically truncated onco-fetal fibronectin isoform expressed by carcinoma and tumor-associated stromal cells.

Migration-stimulating factor (MSF) is a 70-kDa motogenic protein previously reported to be expressed by fetal and cancer patient fibroblasts cultured in vitro and present in the serum of breast cancer patients. A 2.2-kb full-length MSF cDNA has been cloned and shown to be a truncated isoform of fibronectin generated from its primary gene transcript by a hitherto unrecognized intron read-through mechanism. MSF cDNA is identical to the 5' end of fibronectin cDNA, up to and including exon III-1a, and terminates in a novel 195-nucleotide 3' sequence. This MSF unique sequence is derived from the intron immediately downstream of exon III-1a in the fibronectin gene and is not found in any previously identified "full-length" fibronectin cDNA. MSF mRNA is 1000-fold less abundant than full-length fibronectin message in fetal fibroblasts and exhibits rapid biphasic decay kinetics previously associated with oncogenes and stress response molecules. MSF recombinant protein exhibits a potent and substratum-dependent motogenic activity, with half-maximal response manifest at 0.1-1.0 pg/ml. This activity is (a) mediated by the IGD amino acid motif; and (b) not expressed by (i.e., cryptic within) full-length fibronectin. In situ hybridization and immunohistochemistry confirm that MSF is expressed by tumor-associated fibroblasts and additionally indicate that it is also expressed by carcinoma cells and tumor-associated vascular endothelial cells. MSF, as a consequence of its potent bioactivities and expression by both stromal and carcinoma cell populations, is well placed to function as an epigenetic effector promoting cancer development.

Amino Acid Sequence↗