Identification and characterization of a novel member of the fibroblast growth factor family.

A new member of the fibroblast growth factor (FGF) family, FGF-13, has been molecularly cloned as a result of high throughput sequencing of a human ovarian cancer cell library. The open reading frame of the novel human gene (1419 bp) encodes for a protein of 216 a.a. with a molecular weight of 22 kDa. The FGF-13 sequence contains an amino-terminal hydrophobic region of 23 a.a. characteristic of a signal secretion sequence. FGF-13 is most homologous, 70% similarity at the amino acid level, to FGF-8. Northern hybridization analysis demonstrated prominent expression of FGF-13 in human foetal and adult brain, particularly in the cerebellum and cortex. In proliferation studies with BaF3 cells, FGF-13 preferentially activates cell clones expressing either FGF receptor variant, 3-IIIc or 4. The signal transduction pathways of FGF-13 and FGF-2 were compared in rat hippocampal astrocytes. The two FGFs induce an equivalent level of tyrosine phosphorylation of mitogen-activated protein kinase (MAPK) and c-raf activation. However, FGF-13 is more effective than FGF-2 in inducing the phosphorylation of phospholipase C-gamma (PLC-gamma). Treatment of neuronal cultures from rat embryonic cortex with FGF-13 increases the number of glutamic acid decarboxylase immunopositive neurons, the level of high-affinity gamma-aminobutyric acid (GABA) uptake, and choline acetyltransferase enzyme activity. The GABAergic neuronal response to FGF-13 treatment is rapid with a significant increase occurring within 72 h. We have identified a novel member of the FGF family that is expressed in the central nervous system (CNS) and increases the number as well as the level of phenotypic differentiation of cortical neurons in vitro.

Overlapping expression and redundant activation of mesenchymal fibroblast growth factor (FGF) receptors by alternatively spliced FGF-8 ligands.

FGF-8 is a member of the family of fibroblast growth factors and is expressed during vertebrate embryo development. Eight potential FGF-8 isoforms are generated by alternative splicing in mice, several of which are expressed during embryogenesis in epithelial locations. The significance of the multiple isoforms is currently unknown. In this report, we investigate the expression patterns and the specificity of the FGF-8 isoforms for known fibroblast growth factor (FGF) receptors. RNAs for seven of the eight potential isoforms are present at multiple sites of embryonic Fgf8 expression. None of the FGF-8 isoforms exhibited activity when assayed with BaF3 cells expressing the "b" splice forms of FGF receptors 1-3, which are mostly expressed in epithelial tissues. Mesenchymally expressed "c" splice forms of FGF receptors 2 and 3 and FGF receptor 4 were activated by several FGF-8 isoforms. These findings are consistent with the hypothesis that the multiple FGF-8 isoforms are functionally redundant and function to signal in paracrine (epithelial to mesenchymal) contexts.

Effects of cadaver dissection on the attitudes of medical students.

A study was conducted to determine whether the attitudes of medical students to death and caring changed during the 3 months following exposure to cadaver dissection. All first-year students were invited to complete a questionnaire immediately before their initial cadaver dissection experience, after 6 weeks, and after a further 3 months. The questionnaire reflected attitudes to death, violent death, death of someone known to the respondent and caring when someone known to the respondent is seriously injured. Ethnicity and previous exposure to dying has no effect on responses, but overall men students' reactions were significantly less than for women (P < 0.001). The responses given on the final part of the questionnaire after 3 months were significantly lower than those to most questions in the first part of the questionnaire. The exceptions were those questions where the subject in the given scenario was known to the respondent, where reactions were rated significantly greater (P < 0.001) in the follow-up questionnaire and can be explained on the basis that they were a personal referent. Students rapidly develop a coping mechanism which enables them to view cadaver dissection as an occupation quite divorced from living human beings. During these early months of training solicitude decreases for those who die who are unknown to them, but concern for personal referents increases. Educators should be aware of the dramatic change of attitudes among students and the process of professionalization which might influence their caring of future patients.