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F Collins

Publications and source records attributed to F Collins.

At least 91 records · Page 5Linked to original sources

The role of dihydropyridine-sensitive voltage-gated calcium channels in potassium-mediated neuronal survival.

The survival of isolated neurons from chick embryo ciliary, sympathetic, and dorsal root ganglia is greatly enhanced by concentrations of extracellular potassium that significantly depolarize the neurons (ED50 = 20-25 mM). The survival-promoting effect of elevated potassium on each of these 3 types of neurons appears to be the result of the opening of voltage-gated calcium channels. The dihydropyridine, Bay K 8644, which increases calcium influx through L-type voltage-gated calcium channels in neurons, strongly potentiated the survival-promoting action of elevated potassium (ED50 = 10.8 +/- 7.0 nM). In contrast, chemically closely related dihydropyridines, PN200-110 (ED50 = 0.33 +/- 0.15 nM) and nitrendipine (ED50 = 1.3 +/- 0.3 nM), which block calcium influx through the same voltage-gated channels, completely inhibited potassium-mediated neuronal survival. Chemically different agents that also block calcium influx through voltage-gated channels also inhibited potassium-mediated neuronal survival: the phenylalkylamine verapamil (ED50 = 0.78 +/- 0.38 microM), the benzothiazepine diltiazem (ED50 = 1.7 microM), and the inorganic ion cadmium (ED50 = 5.8 microM). These calcium-channel blockers are not simply toxic to neurons, since they did not inhibit neuronal survival mediated by the neurotrophic proteins, nerve growth factor, basic fibroblast growth factor, or ciliary neurotrophic factor, also suggesting that voltage-gated calcium channels are not involved in the action of these factors. These results suggest that neuronal survival in elevated potassium in ciliary, sympathetic, and dorsal root ganglion neurons is the result of calcium influx through dihydropyridine-sensitive, L-type voltage-gated calcium channels. These findings are discussed in relation to the neuronal toxicity of excitatory amino acids which is also thought to occur through increased calcium influx.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Sustained elevation in hippocampal NGF-like biological activity following medial septal lesions in the rat.

Several laboratories have documented an increase in hippocampal nerve growth factor (NGF) levels, measured with biological or immunological assays, within 1-2 weeks following septal lesions or fimbria/fornix transections. In the present study we have determined the increase in NGF-like biological activity in medium conditioned by hippocampal slices at more prolonged times following medial septal lesion. In contrast to reports based on immunological assays, which demonstrate a transient increase in hippocampal NGF, elevated NGF-like biological activity was present in hippocampal slice-conditioned medium up to one year after a medial septal lesion.

Animals↗

Differences in the plasma concentrations of FSH and LH in ovariectomized Booroola FF and ++ ewes.

During 12 sampling days before ovariectomy the mean plasma FSH but not LH concentrations in FF ewes were higher (P less than 0.01) than those in ++ ewes (16 ewes/genotype). After ovariectomy increases in the concentrations of FSH and LH were noted for ewes of both genotypes within 3-4 h and the rates of increase of FSH and LH were 0.18 ng ml-1 h-1 and 0.09 ng ml-1 h-1 respectively for the first 15 h. From Days 1 to 12 after ovariectomy, the overall mean +/- s.e.m. concentrations for FSH in the FF and ++ ewes were 8.1 +/- 0.6 and 7.1 +/- 0.4 ng/ml respectively and for LH they were 2.7 +/- 0.3 and 2.1 +/- 0.2 ng/ml: these differences were not statistically significant (P = 0.09 for both FSH and LH; Student's t test). However, when the frequencies of high FSH or LH values after ovariectomy were compared with respect to genotype over time, significant F gene-specific differences were noted (P less than 0.01 for both FSH and LH; median test). In Exp. 2 another 21 ewes/genotype were blood sampled every 2nd day from Days 2 to 60 after ovariectomy and the plasma concentrations of FSH and LH were more frequently higher in FF than in ++ ewes (P less than 0.01 for FSH and LH). The F gene-specific differences in LH concentration, observed at 21-36 days after ovariectomy were due to higher mean LH amplitudes (P less than 0.025) but not LH peak frequency in FF than in ++ ewes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Effects of oestradiol-17 beta, progesterone or bovine follicular fluid on the plasma concentrations of FSH and LH in ovariectomized Booroola ewes which were homozygous carriers or non-carriers of a fecundity gene.

The plasma concentrations of FSH and LH were measured in ovariectomized Booroola FF and ++ ewes before and after treatment with subcutaneous implants of oestradiol-17 beta (0, 2 or 8 cm Silastic capsules; 5 ewes/genotype per dose) or progesterone (0, 1 or 3 Silastic envelopes; 5 ewes/genotype per dose) or subcutaneous injections of steroid-free bovine follicular fluid (bFF; 0, 0.5, 1.0, 2.5 or 5 ml; 4 ewes/genotype per dose). During the first 50 h after implantation of oestradiol or progesterone, or the first 24 h after bFF treatment, the FSH and LH concentrations in plasma were not different between the genotypes although there were significant effects of the steriods and bFF with respect to dose (P less than 0.05). At 6 days after steroid implantation, no gene-specific effects were noted for the plasma concentrations of FSH although significant effects of dose of oestradiol (P less than 0.01) but not progesterone were noted. Also at 6 days after steroid implantation, no gene-specific differences in the pulsatile patterns (i.e. peak frequency or amplitude) of plasma LH concentrations were noted although there were significant effects of steriod dose (P less than 0.05) on frequency and/or amplitude. It is concluded that the higher ovulation-rate in FF than ++ Booroola ewes is unlikely to be due to gene-specific differences in the sensitivity of the hypothalamic-pituitary axis to ovarian hormones.

Animals↗

Developmental time course of the effect of nerve growth factor on the parasympathetic ciliary ganglion.

Neurite outgrowth in the presence and absence of nerve growth factor (NGF) was compared in neuronal cultures from the parasympathetic ciliary ganglion and from a traditional target of NGF, the sensory dorsal root ganglion. Both ciliary and dorsal root ganglion cultures exhibited a developmental time window during which the effect of NGF on neurite length was maximal. Although neuronal cultures from embryonic day 4 and 5 ganglia exhibited considerable neurite outgrowth in the absence of NGF, there was no significant increase in neurite outgrowth in the presence of NGF. After embryonic day 6, there was a steady increase in the effect of NGF in both types of ganglia. With ciliary ganglia, the effect of NGF increased until day 8, plateaued, then fell off significantly after day 11. With dorsal root ganglia, the effect of NGF continued to increase until day 12, plateaued, then fell off significantly after day 17. Thus, the period of maximal responsiveness of chick ciliary ganglia to NGF occurs earlier in development than for dorsal root ganglia. At the ages when the effect of NGF was maximal, approximately 20% of ciliary ganglion neurons exhibited substantial increases in neurite length compared to approximately 40% of dorsal root ganglion neurons. The effect of NGF was maximal at or below 1 ng/ml (4 X 10(-11) M) for both types of ganglia. These results support previous evidence that NGF does not simply boost ciliary ganglionic neurite growth non-specifically: the effect of NGF is already maximal at low, physiological concentrations and it appears at a specific time in development.

Animals↗

Localisation of the endpoints of deletions in the 5' region of the Duchenne gene using a sequence isolated by chromosome jumping.

We have used chromosome jumping technology to move from within a large intron sequence in the Duchenne muscular dystrophy (DMD) gene to a region adjacent to exons of the gene. The single copy jump clone, HH1, was used to characterise deletions in patients previously shown to be deleted for DNA markers in the 5' end of the gene. 12 out of 15 such patients have breakpoints which lie between HH1 and the genomic locus J-47. Thus the vast majority of the deletions in these patients have proximal breakpoints in a similar region distal to the 5' end of the gene. HH1 was mapped with respect to the X;1 translocation in a DMD female and was shown to lie at least 80 kb from the starting point of the chromosome jump, HIP25.

Cell Line↗

Corresponding spatial gradients of TOP molecules in the developing retina and optic tectum.

The topographic map of cell position in the avian retina is inverted in its projection to the optic tectum. Dorsal retinal ganglion cell axons project to ventral tectum, and ventral retinal ganglion cells project to dorsal tectum. Topographic gradients of toponymic (TOP) cell surface molecules along the dorsoventral axes of retina and tectum also are inverted. TOP molecules are most abundant in dorsal retina and ventral tectum and least abundant in ventral retina and dorsal tectum during the period of initial retinal-tectal interaction. Thus, TOP molecules may be involved in orienting the retinotectal map.

Animals↗

Malignant melanotic schwannoma of the bronchus.

A case of malignant melanotic schwannoma arising in the right upper lobe bronchus of a 27 year old man is presented. Tumours of this type most commonly occur in spinal nerve roots and are generally considered to be benign. The behaviour of those originating elsewhere is less predictable. As far as we are aware this is the first reported case affecting the respiratory tract.

Adult↗

Physicians and administrators: inducing collaboration.

This article examines conflict between hospital administrators and physicians, which has been exacerbated by prospective reimbursement, rising health care costs, and scarce resources. Within the context of a hospital setting, conflict is viewed as being three phases: frustration, conceptualization of issues and outcomes, and behavior. Once physicians consciously realize conflict exists between themselves and an administrator, they will begin to conceptualize their frustration. Conceptualization leads to various forms of behavior toward the administrator, depending on the physicians' desires to satisfy both their own needs and the needs of the administrator. Use of a systems oversight committee composed of physicians and administrators can help conceptualization occur positively--a key factor in inducing collaborative behavior. Collaboration between administrators and physicians is most beneficial in achieving long-term goals and objectives. To promote collaboration, a physician-administrator oversight committee is proposed to help physicians realize that their success depends on supportive relationships with hospital administration.

Conflict, Psychological↗

Entorhinal lesions result in increased nerve growth factor-like growth-promoting activity in medium conditioned by hippocampal slices.

Nerve growth factor (NGF) is present in high concentrations in the rat hippocampal formation where it may be involved in sympathetic sprouting following septohippocampal denervation. In addition, recent evidence suggests that some forebrain cholinergic neurons, including septohippocampal neurons, are responsive to exogenous NGF. Since septohippocampal neurons have been shown to sprout in response to entorhinal lesions both in rats and, recently, in humans, we sought to determine whether endogenous NGF-like activity increases in the rat hippocampal formation following injury to the entorhinal cortex. We found that entorhinal lesions which result in extensive denervation of the dentate granule cells, and subsequent sprouting of septohippocampal axons, do result in greater NGF-like growth-promoting activity in medium conditioned by slices of the denervated tissue when compared to medium conditioned by control tissue. These results suggest that brain NGF may be involved in injury-induced sprouting of forebrain cholinergic neurons.

Acetylcholinesterase↗

Electrophoretic similarity of the ciliary ganglion survival factors from different tissues and species.

The survival of dissociated ciliary ganglion neurons is promoted by extracts of several different embryonic and adult tissues from two species. The survival-promoting activity in each of these extracts survives exposure to sodium dodecyl sulfate (SDS) and sulfhydryl-reducing agent and can, therefore, be subjected to SDS-polyacrylamide gel electrophoresis. Upon electrophoresis, the survival-promoting activity is recovered in a discrete peak at an apparent molecular weight of approximately 21,800 for all of the tissues examined. These results suggest that a similar molecule in each of these different tissues and species may be responsible for their ability to promote the survival of ciliary ganglion nerve cells in culture.

Animals↗

Neurotrophic activity in the adult rat hippocampal formation: regional distribution and increase after septal lesion.

Conditioned medium prepared from slices of the rat hippocampal formation contains an agent that shares the following properties with nerve growth factor (NGF): it promotes neurite growth from embryonic sympathetic ganglia in vitro; and it is inhibited by affinity-purified antibody against mouse submaxillary gland 2.5 S NGF. The NGF-like growth-promoting activity is regionally distributed within the hippocampal formation: the activity is consistently higher in the dentate gyrus-CA3 region than in the CA1 region. Furthermore, the level of activity is significantly increased within 1 week after a medial septal lesion, and, in the dentate-CA3 region, the increased level of activity is maintained for at least 4 weeks after the lesion. Control lesions that fail to interrupt the septohippocampal innervation, but cause equally extensive damage to nearby regions of the central nervous system, do not cause increased levels of activity in the hippocampal formation. These results provide substantial evidence linking the NGF-like agent in hippocampal conditioned medium to the sprouting of sympathetic axons into the dentate gyrus-CA3 region of the hippocampal formation after a medial septal lesion in vivo.

Animals↗

The spatial control of ganglionic neurite growth by the substrate-associated material from conditioned medium: an experimental model of haptotaxis.

Techniques are described for forming on the culture substrate a narrow pathway of material derived from medium conditioned by embryonic non-neuronal cells. There is a precise correlation between the known location of the pathway and the spatial distribution of neurites extended from whole ciliary ganglia or dissociated neurons grown on the patterned substrate. When individual growth cones moving on the pathway contact one of its edges, they turn sharply so as to remain on the pathway. This turning response is not simply due to a physical barrier to movement across the edge, since growth cones can cross onto the pathway when entering from the adjacent untreated substrate. The strong preference for neurites to maintain contact with the pathway also is not simply a result of their inability to survive or elongate outside of the pathway, since neurites from whole ganglia elongate readily on other regions of the substrate, although their growth is then undirected. Direct contact with the pathway is required for these directive effects, and there is no indication that the material bound to the substrate diffuses off and exerts its effects at a distance. The neurite-guiding activity is found in partially purified fractions of conditioned medium which also contain a substrate-bound inducer of neurite outgrowth. It is possible that both activities may be due to the same components of conditioned medium. These results suggest that ciliary ganglion growth cones are able to detect specific components of conditioned medium on the substrate and respond to their presence by changing their direction of movement so as to remain in contact with these components.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

An effect of nerve growth factor on the parasympathetic ciliary ganglion.

Mouse submaxillary nerve growth factor (NGF) increases the length and density of neurites extended from embryonic chick ciliary ganglia in vitro. The effect is not as pronounced as with dorsal root ganglia, but it occurs at the same low concentrations of NGF. This effect was observed on polyornithine substrata with or without pretreatment of the substratum with conditioned medium. NGF did not significantly increase the length or density of neurites extended from spinal cord or neural retina explants in the same culture conditions. Stimulation of ciliary ganglion neurite outgrowth did not occur when NGF was replaced with cytochrome c or epidermal growth factor, whereas insulin had an effect comparable to that of NGF when present at much higher concentrations. Four different purified preparations of NGF gave identical results. The purity of two of these preparations was determined after radioiodination; greater than 98% of the radioactivity migrated as a single band on polyacrylamide gels, and greater than 94% of the radioactivity was bound by affinity purified anti-NGF antibody. The effect of NGF on neurite growth could be separated from its effect on neuronal survival. NGF failed to promote the survival of ciliary ganglion neurites even at concentrations 1000-fold higher than those which significantly stimulated neurite growth.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

An effect of nerve growth factor on parasympathetic neurite outgrowth.

Addition of nerve growth factor (NGF) to dissociated parasympathetic ciliary ganglion neurons resulted, within 60 min of its addition, in a 2-fold increase in average neurite length and an accompanying enlargement and spreading of neuronal growth cones. These effects occurred over a concentration range of NGF of 0.1-10 ng/ml and were blocked by affinity-purified antibody to NGF. Epidermal growth factor, fibroblast growth factor, and angiotensin did not have these effects, although insulin at high concentrations was able to induce a response similar to that of NGF. Dissociated sympathetic chain neurons also responded to NGF with increased neurite lengths, and, in addition, NGF considerably extended the survival time of these neurons in culture. However, the effect of NGF on ciliary ganglion neurons was limited to neurite outgrowth, and NGF did not promote the survival of these parasympathetic neurons.

Animals↗