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Biomedical subjects

A Fisher

Publications and source records attributed to A Fisher.

At least 235 records · Page 13Linked to original sources
PubMed1982

Long-term central cholinergic hypofunction induced in mice by ethylcholine aziridinium ion (AF64A) in vivo.

Ethylcholine mustard aziridinium ion (AF64A), a neurotoxic choline analog, was evaluated for its interactions with the cholinergic system in mice. Parenterally administered AF64A was lethal (LD50 = 32.6 mumol/kg i.v.) and the lethality could be antagonized even at 8 LD50 doses by pretreatment with choline (714 mumol/kg i.p.) 2 min earlier. Mice that were protected by choline slowly developed neurological motor disturbances such as ataxia and hypokinesia, and lost weight. Intracerebroventricular administration of 65 nmol of AF64A was not acutely lethal, but produced similar delayed behavioral effects similar to those found after parenteral administration of AF64A. Seven days after a single injection of 65 nmol of AF64A i.c.v., there was a significant decrease in acetylcholine content in the cortex, striatum and hippocampus, but no change in choline levels. Acetylcholine content was still significantly reduced in the hippocampus at 3 weeks after this treatment. The reduction in activity of choline acetyltransferase and high-affinity choline transport paralleled the reduction in acetylcholine measured at 7 days post AF64A treatment, whereas muscarinic receptors in all three brain areas were unchanged. These combined data indicate that AF64A is a presynaptic chemical neurotoxin, capable of inducing a persistent deficiency in central cholinergic transmission.

Acetylcholine↗
PubMed1981

The AF64a-treated mouse: possible model for central cholinergic hypofunction.

A loss in the number of functional, sodium ion-dependent, high-affinity choline transport sites was observed in the cortex and hippocampus of mice given an intracerebroventricular injection of 65 nanomoles of AF64A (ethylcholine mustard aziridinium ion) 3 days earlier. Such an effect was not observed in the striatum. This effect of AF64A represents a long-term neurochemical deficit at cholinergic nerve terminals in some brain regions which can lead to a persistent deficiency in central cholinergic transmission. The AF64A-treated animal may thus be a model for certain psychiatric or neurological disorders that appear to involve central cholinergic hypofunction.

Animals↗
PubMed1981

Repair of the injured spleen.

Splenic laceration is the most frequent visceral injury requiring laparotomy after blunt abdominal trauma in children. Splenectomy increases the risk of overwhelming bacterial infection which could prove fatal. This paper reports four patients with splenic injury who were treated by splenic repair.

Adult↗
PubMed1981

Effects of infraorbital nerve section on survival, growth, and suckling behaviors of developing rats.

Previous studies on sensory control of nursing in the rat have emphasized local olfactory cues. This study examined the role of tactile sensory processes by surgical section of the infraorbital nerve in rats at 17, 12, 7, and less than 1 day of postnatal age. All sectioned rats showed anesthesia of snout, upper lip, and vibrissal pads, and severe impairment of nipple attachment for at least the first day after denervation. Seven-day-old pups failed to recover, and all died after 3-6 days of relentless weight loss. Seventeen-day-old pups showed no weight loss after denervation if already weaned to solid food, but they lost weight for 3 days, and 25% failed to recover. Behavioral observations showed that denervated pups were activated by the mother's ventrum and probed for the nipple in the appropriate area but failed to focus head sweeping or licking and mouthing on the nipple itself and did not attach even when the nipple was inserted into the intact sensory areas of the mouth. Recovery after nerve section did not appear to be due to nerve regeneration. The data show that tactile cues are not necessary for normal nursing in the rat and suggest that important tactile sensorimotor adaptations may occur during the early and late phases of nursing.

Afferent Pathways↗
PubMed1980

Amyloid neuropathy and tremor in Waldenström's macroglobulinemia.

We report a case of Waldenström's macroglobulinemia with amyloid neuropathy and a parkinsonian syndrome. We describe the light and electron microscopic findings in a sural nerve biopsy specimen and discuss the possible pathogenic mechanisms in the production of the neuropathy. In contrast to a number of previous cases of neuropathy associated with Waldenström's macroglobulinemia, evidence of immunoglobulin deposition on nerve fibers was not found using immunofluorescent techniques.

Amyloidosis↗
PubMed1980

Does rigidity in structure of muscarinic agonists and antagonists reflect drug specificity?

The present work is an attempt to elucidate: (1) whether highly rigid structural analogs of acetylcholine are still capable of activating the muscarinic receptor; (2) whether such analogs, be they agonists or antagonists, discriminate among the various ACh-mediated functions, thereby providing a tool for the study of a possible receptor heterogeneity; (3) whether structural rigidity is a significant factor in the kinetics of drug-receptor interaction. To this end, we investigated some properties of drugs in the spiro-(1,3-dioxolane-4,3')-quinuclidine system (SDQ) which embodies the muscarinic pharmacophore in a framework of utmost rigidity. Wherever possible, these properties were compared with those of a closely related but more flexible analog. Variation in effect between members of a rigid-flexible pair or among drugs of varying rigidity is considered to reflect varying affinities towards various sites of action. 2-Methyl-spiro-(1,3-dioxolane-4,3')-quinuclidine (AF-30) is a weak but selective muscarinic agonist. It can be viewed as a highly rigid version of 3-acetoxyquinuclidine (3-AcQ) and it can be used as a probe for detection of heterogeneity among muscarinic receptors. AF-30 is equipotent with 3-AcQ in causing tremors (mice), but has 1/17th the activity of 3-AcQ in the guinea-pig ileum, 1/30th in lowering blood pressure (cats) and 1/10th in inducing analgesia (mice). 2-Diphenylmethyl-spiro(1,3-dioxolane-4',3)-quinuclidine (AF-41) and 2.2-diphenyl-spiro-(1,3-dioxolane-4,3')-quinuclidine (AF-32 are potent antagonists and possess KD values in the same range as those of the more flexible congener 3-diphenylacetoxy-quinuclidine (AF-43) and atropine (0.6--2 nM) but with koff = 0.1 msec-1 (AF-41) and koff = 1 msec-1 (AF-43) (carp atrium). Thus, duration of drug action of drug action at the receptor is a function of structural rigidity in the drug molecule, termination of action being fastest with the flexible molecules. Differences in rigidity among various antagonists also find expression in an unequal distribution of potencies in various tests; thus the rigid antagonists differentiate between two central effects in mice, viz., prevention of oxotremorine-induced tremors and fall from the rotating rod by a factor of 1:20 (especially AF-41 versus AF-43), whereas the more flexible antagonists (AF-43, atropine or even 3-quinuclidinyl-benzilate) do not show such as a selectivity. The existence of heterogenous muscarinic receptors can be inferred from data presented. Both theoretical and practical implications are discussed.

Acetylcholine↗
PubMed1979

Offset rate of action of muscarinic antagonists depends on their structural flexibility.

Time course measurements of the action of muscarinic antagonists were performed in the spontaneously beating carp atrium. Several high affinity drugs, which embody the quinuclidine structure were examined. The structural flexibility of these molecules was reflected in the dissociation of the drugs from the muscarinic receptor. The dissociation of rigid drugs was very much prolonged as compared to flexible drugs of the same affinity.

Acetylcholine↗
PubMed1979

Observations on voluntary nystagmus.

Unitl recent times, reports concerning voluntary nystagmus have been dismissive, most observers regarding the phenomenon as a form of ocular acrobatics or an amusing party trick. The introduction of sophisticated recording apparatus coupled with renewed interest in ocular kinetics has resulted in a more analytical approach. Clinical and electro-oculographic study of the condition in 5 subjects was undertaken in an attempt to relate voluntary nystagmus to the known mechanisms of oscular movement control. The frequency of the movement varied from 15 to 23Hz and amplitude from 2 to 5 degrees. The wave form was similar to that seen in acquired pendular nystagmus. It was concluded that, depsite differences in frequency, the similarity in form of the movements of voluntary nystagmus and acquired pendular nystagmus suggested a possible identity in the mechanisms of the movements.

Adult↗
PubMed1978

Changes in plasma catecholamines and dopamine beta-hydroxylase after corrective surgery for coarctation of the aorta.

In six patients within 12 hours of surgical correction of aortic coarctation there was a 750% increase in plasma noradrenaline concentrations accompanied by an increase in systolic and diastolic blood pressures. The magnitude of the postoperative increase in noradrenaline concentrations was related to the preoperative level of the pressure gradient across the coarctation. Six months after operation plasma noradrenaline concentrations were still significantly elevated. In nine patients who underwent other types of major surgery there was a small increase in plasma noradrenaline concentrations and a return to levels within the normal range within 24 hours. Various explanations for the rise in plasma noradrenaline concentrations are considered. In particular the possibility is raised that after surgical correction of aortic coarctation the increased levels indicate a marked increase in sympathetic nervous system activity; this may be mediated by baroreceptor mechanisms and may persist for up to six months after surgery.

Adolescent↗