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J Furness

Publications and source records attributed to J Furness.

14 recordsLinked to original sources
PubMed1994

Activation of the FGF receptor underlies neurite outgrowth stimulated by L1, N-CAM, and N-cadherin.

Cell contact-dependent neurite outgrowth stimulated by CAMs requires activation of a second messenger pathway that requires the function of a tyrosine kinase upstream from calcium influx into neurons. In the present study, we present evidence that implicates activation of the fibroblast growth factor receptor (FGFR) in the pathway underlying neurite outgrowth stimulated by L1, N-CAM, and N-cadherin. We have identified a CAM homology domain in the FGF family of receptors and show that antibodies which bind to this domain specifically inhibit neurite outgrowth stimulated by the above CAMs. We also show that synthetic peptides derived from this domain can differentially and specifically inhibit neurite outgrowth stimulated by L1, N-CAM, and N-cadherin. In addition, a soluble L1-Fc chimera is shown to stimulate an increase in phosphotyrosine on the same set of neuronal proteins that are phosphorylated following activation of the FGFR with basic FGF.

Amino Acid Sequence↗
PubMed1994

Neurite outgrowth stimulated by the tyrosine kinase inhibitor herbimycin A requires activation of tyrosine kinases and protein kinase C.

Activation of tyrosine kinases is established as an important mechanism for controlling growth cone motility and neurite outgrowth. We have tested the effects of a range of tyrosine kinase inhibitors on neurite outgrowth from postnatal day 4 cerebellar granule cells cultured over confluent monolayers of 3T3 fibroblasts. The only agent that had any effect was herbimycin A, which stimulated neurite outgrowth. The response is shown to be attributable to a direct effect of this tyrosine kinase inhibitor on neurones. The neurite outgrowth response to herbimycin A was inhibited by two other tyrosine kinase inhibitors, which on their own did not affect neurite outgrowth. The data suggest that the response to herbimycin A reflects either a direct or indirect activation of one or more protein tyrosine kinases. Independent signalling events down-stream from tyrosine kinase activation underlying the neurite outgrowth response to herbimycin A include increased activity of protein kinase C and calcium influx into neurones through both N- and L-type calcium channels.

Animals↗
PubMed1994

Characterisation of the second messenger pathway underlying neurite outgrowth stimulated by FGF.

Cerebellar neurons, cultured on monolayers of 3T3 fibroblasts or on a polylysine/laminin-coated substratum, responded to recombinant basic FGF by extending longer neurites. The response was biphasic reaching a maximum at 5 ng/ml FGF, but desensitising at 100-200 ng/ml FGF. The response to FGF could be inhibited by a tyrosine kinase inhibitor (the erbstatin analogue), by a diacylglycerol lipase inhibitor (RHC-80267) and by a combination of N- and L-type calcium channel antagonists or other agents that negate the effects of calcium influx into neurons. The response to FGF could be fully mimicked by arachidonic acid added directly to the cultures, or generated via activation of phospholipase A2 with melittin. The response to melittin, but not to FGF or arachidonic acid, was inhibited by 4-bromophenacyl bromide, a phospholipase A2 inhibitor. The response to arachidonic acid was also biphasic and high concentrations of this agent could cross-desensitise the FGF response and vice versa. The response to arachidonic acid could be fully inhibited by the agents that block or negate the effects of calcium influx into neurons, but was not inhibited by the tyrosine kinase or diacylglycerol lipase inhibitors. These data suggest that FGF stimulates neurite outgrowth by activating a cascade that involves activation of phospholipase C gamma to produce diacylglycerol, conversion of diacylglycerol to arachidonic acid by diacylglycerol lipase and the activation of voltage-gated calcium channels by arachidonic acid.

3T3 Cells↗
PubMed1992

Use of the neural cell adhesion molecule VASE exon by neurons is associated with a specific down-regulation of neural cell adhesion molecule-dependent neurite outgrowth in the developing cerebellum and hippocampus.

The development of the CNS is associated with an increasing use of the 30-bp variable alternative, spliced exon (VASE) in neural cell adhesion molecule (NCAM). We have assessed the relative usage of VASE by reverse transcriptase-linked polymerase chain reaction in the developing cerebellum and hippocampus at times when neurons isolated from these tissues can respond to substrate-associated NCAM by increased axonal growth and also at later developmental stages, when they are no longer responsive to substrate-associated NCAM. Neurons isolated from the developing cerebellum at postnatal day 6 respond to NCAM with increased neurite growth. NCAM transcripts from these cells were found to have negligible levels of VASE usage. In contrast, neurons that are isolated at later stages of development (postnatal days 8, 10, and 11) and do not respond to NCAM were found to synthesise a much higher proportion of NCAM transcripts containing VASE. In the hippocampus, embryonic day 18 neurons, which are responsive to NCAM, express low levels of VASE, whereas postnatal days 4 and 5 neurons, which are not responsive to NCAM, have a greater proportion of transcripts containing VASE. Thus, the level of NCAM VASE exon usage by neurons appears to be a good indicator of the ability of these cells to respond to non-VASE-containing NCAM (expressed in a cellular substratum) by increased neurite outgrowth.

Alternative Splicing↗
PubMed1981

A general review of bite-mark evidence.

Bite-mark evidence has been used as an aid in the identification of criminals in many instances. The author, a forensic odontologist in Liverpool, England, during his lifetime, personally investigated the cases presented which include instances of rape and battery. It is shown how perpetrators of violent injuries were detected from bite marks on the victim or the perpetrator, or on foodstuffs found at the scene of the crime, when the marks were compared to dental impressions taken subsequently.

Battered Child Syndrome↗
PubMedDate not supplied

Adrenaline synthesizing nerve cells in the medulla of normotensive and hypertensive rats.

1. We have studied the number and distribution of adrenaline synthesizing nerve cells in the medulla oblongata of the rat, using a combination of immunofluorescence to visualize the enzyme phenylethanolamine-N-methyltransferase (PNMT) and catecholamine fluorescence to detect central catecholamines. 2. The distribution of adrenaline synthesizing nerve cells was similar in normotensive (Wistar Kyoto) rats, spontaneous hypertensive rats, and stroke-prone rats. Few of the cells visualized by PNMT immunofluorescence were detected by the Faglu fluorescence method for catecholamines. The C1 (ventrolateral) and C2 (dorsomedial) groups of PNMT cells were anatomically distinct from the A1 and A2 groups of catecholamine fluorescent cells and lay rostral to these cells within the medulla. There was a third group of adrenaline synthesizing cells close to the midline in the rostral medulla, and we have called this the C3 group. 3. There was a 32% increase in the number of PNMT cells in the medulla of 4-week-old stroke-prone rats. 4. PNMT enzyme activity in a cross-segment of the medulla containing the adrenaline synthesizing cells was also increased by 30% in both spontaneous hypertensive rats and stroke-prone rats.

Animals↗
PubMedDate not supplied

Forensic odontology.

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Bites and Stings↗