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Biomedical subjects

L B Geffen

Publications and source records attributed to L B Geffen.

At least 55 records · Page 3Linked to original sources
PubMed1979

Immune lesions of central noradrenergic neurons produced by antibodies to dopamine-beta-hydroxylase.

(1) Intraventricular injection of antibodies to dopamine-beta-hydroxylase (DBH) caused degeneration of central noradrenergic nerve terminals in rats and guinea-pigs. In rats it was necessary to infuse exogenous complement in the form of guinea-pig serum together with the anti-DBH, whereas in guinea-pigs the anti-DBH was effective on its own. Control animals were infused with equivalent amounts of non-immune serum and complement and showed no signs of degeneration other than in the region of the needle tract. (2) There was a loss of varicosities in most terminal fields of the noradrenergic projections and swollen distorted axons were seen in both ascending and descending noradrenergic pathways. Noradrenergic cell bodies in the locus coeruleus and subcoeruleus appeared unaffected. No histochemical changes were observed in dopaminergic neurons. (3) The ultrastructural changes in degenerating axons that were first identifided by fluorescence histochemistry included swelling, vacuolation, accumulation of dense cored vesicles, lysosome-like bodies and smooth membranous sacs. The surrounding neuropil appeared normal. (4) There was a significant depletion of noradrenaline in all regions of the rat brain ranging from 20% in the hypothalamus to 80% in the neocortex. Dopamine concentrations were unaffected. (5) These observations provide a new approach to the production of selective lesions in specific neurotransmitter pathways that could be extended to non-adrenergic neurones. They may also be useful as a model for the study of autoimmune diseases of the nervous system.

Animals↗
PubMed1979

Noradrenergic transmission in isolated guinea-pig intestine following in vivo administration of antibodies to dopamine beta-hydroxylase.

The effectiveness of transmission from noradrenergic nerves supplying the guinea-pig ileum was evaluated in normal preparations and in preparations taken from animals injected 18 h to 4 days previously with antiserum to dopamine beta-hydroxylase. Degeneration of the nerves following the antiserum was monitored histochemically in the same preparations. A decline in the effectiveness of transmission, which paralleled the degeneration of the nerves, was observed. The earliest effects were detected at 18 h and the greatest effect was found at 2-4 days following the administration of antiserum. Binding of the antibodies has been detected as early as 6 h after injection. It is therefore concluded that binding of the antibodies to the nerves, per se, does not significantly compromise transmission, and that histochemical evidence of degeneration can be used to indicate the onset of functional deterioration of noradrenergic nerves following their exposure to antibodies to dopamine beta-hydroxylase.

Adrenergic Fibers↗
PubMed1977

Involvement of complement in degeneration of sympathetic nerves after administration of antiserum to dopamine beta-hydroxylase.

The involvement of complement in the degeneration of noradrenergic nerves in the guinea-pig iris produced by administration of antibody to dopamine beta-hydroxylase (DBH) in vivo was investigated histochemically. When 500 microliter of antiserum to DBH was injected systemically, no evidence of degeneration was observed in the iris although the noradrenergic supply of the myenteric plexus of the ileum degenerated within 2 days. However, injection of 20 microliter of complement (C) into the anterior chamber of one eye within 2 days of the systemic administration of anti-DBH produced a degeneration of 50--90% of noradrenergic terminals in the iris, the nerves of the iris of the contralateral uninjected eye being unaffected. Electron microscopy confirmed the presence of degenerating nerve terminals in the iris. The extent of degeneration produced by addition of C decreased when C was injected at increasing intervals after the antiserum. Intraocular injection of 5 microliter of anti-DBH together with 20 microliter of C caused a substantial degeneration of noradrenergic nerves in the iris. In contrast, intraocular injection of the Fab'2 fragment of anti-DBH (which did not bind C, but still bound DBH in vitro and in vivo) failed to cause degeneration in the presence of 20 microliter of C. The degeneration of guinea-pig sympathetic nerves caused by antibodies to DBH thus appears to be due to a complement mediated lysis of sympathetic axon membranes. The relative susceptibilities of the noradrenergic fibres in different tissues probably depend on the local concentrations of anti-DBH and C.

Adrenergic Fibers↗
PubMed1972

Rapid axoplasmic transport of tyrosine hydroxylase in relation to other cytoplasmic constituents.

The transport of norepinephrine and two key enzymes involved in its synthesis, tyrosine hydroxylase (EC 1.14.3a) and dopamine beta-hydroxylase (EC 1.14.2.1), has been studied in relation to other axonal constituents in ligated chicken sciatic nerves. Norepinephrine, tyrosine hydroxylase, and dopamine beta-hydroxylase activity all increased proximal to the constriction over a 20-hr period. The rate of transport of norepinephrine, tyrosine hydroxylase, and dopamine beta-hydroxylase were calculated as 2.6, 1.9, and 3.4 mm/hr, respectively. The only enzyme marker to show a similar rate of accumulation was acetylcholinesterase (EC 3.1.1.7), a putative marker for endoplasmic reticulum. The rapid axoplasmic transport of tyrosine hydroxylase from the cell bodies to the terminals of sympathetic neurons may be adequate to account for the elevated amounts of this enzyme in chronically active axon terminals, without the necessity to invoke peripheral axonal synthesis of the enzyme to explain such elevated amounts.

Acetylcholinesterase↗
PubMed1972

Degeneration of sympathetic nerves in vitro and development of smooth muscle supersensitivity to noradrenaline.

1. The sequence of events involved in degeneration of sympathetic nerve terminals has been studied in vitro in the expansor secundariorum muscle of the chicken.2. The muscle underwent a degeneration contraction due to abrupt release of noradrenaline stores from the nerves about 18 hr after isolation. The tension reached its peak within 6 hr at about 44% of the maximum tension developed to added noradrenaline.3. Responses to nerve stimulation were transiently potentiated by 35% on average just before the onset of the degeneration contraction and then failed abruptly.4. Degeneration release of noradrenaline was Ca(2+)-dependent. Development of the degeneration contraction was delayed by temporary withdrawal of Ca(2+) from the medium and was accelerated by a twofold increase in Ca(2+) concentration when applied at a critical period close to the onset.5. Neither continuous nerve stimulation nor alterations in the length of the nerve stump influenced the course of the degeneration contraction in vitro.6. When the muscle was left in situ after denervation, the degeneration contraction occurred between 2 and 3 days later depending on the length of the distal portion of nerve. Cutting the nerve supply 5 cm closer to the muscle in vivo hastened the loss of transmission and the onset of the degeneration contraction by 24-48 hr.7. Supersensitivity to noradrenaline occurred soon after the degeneration contraction but the full development of a sevenfold supersensitivity to noradrenaline, equivalent to that produced by cocaine, took up to 48 hr. No further increase in sensitivity to noradrenaline could be detected in vitro after chronic denervation in vivo for up to 30 days.8. It is concluded that the degeneration contraction and failure of transmission was precipitated by an abrupt increase in the Ca(2+) permeability of the axon causing discharge of transmitter from vesicles. This was probably the result of depletion of essential factors normally transported somatofugally in the axon at 1-2 mm/hr. The supersensitivity to noradrenaline that develops subsequently appears to be due to a loss of the uptake mechanism of the nerve terminals.

Animals↗