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Biomedical subjects

J Greenan

Publications and source records attributed to J Greenan.

11 recordsLinked to original sources
PubMed1996

Age-dependent neuronal and synaptic degeneration in mice transgenic for the C terminus of the amyloid precursor protein.

The molecular basis for the degeneration of neurons and the deposition of amyloid in plaques and in the cerebrovasculature in Alzheimer's disease (AD) is incompletely understood. We have proposed that one molecule common to these abnormal processes is a fragment of the Alzheimer amyloid precursor protein (APP) comprising the C-terminal 100 amino acids of this molecule (APP-C100). We tested this hypothesis by creating transgenic mice expressing APP-C100 in the brain. We report here that aging (18-28 month) APP-C100 transgenic mice exhibit profound degeneration of neurons and synapses in Ammon's horn and the dentate gyrus of the hippocampal formation. Of the 106 transgenic mice between 8 and 28 months of age that were examined, all of those older than 18 months displayed severe hippocampal degeneration. The numerous degenerating axonal profiles contained increased numbers of neurofilaments, whorls of membrane, and accumulations of debris resembling secondary lysosomes near the cell body. The dendrites of degenerating granule and pyramidal cells contained disorganized, wavy microtubules. Cerebral blood vessels had thickened refractile basal laminae, and microglia laden with debris lay adjacent to larger venous vessels. Mice transgenic for Flag-APP-C100 (in which the hydrophilic Flag tag was fused to the N terminus of APP-C100) showed a similar degree of neurodegeneration in the hippocampal formation as early as 12 months of age. The 45 control mice displayed only occasional necrotic cells and no extensive cell degeneration in the same brain regions. These findings show that APP-C100 is capable of causing some of the neuropathological features of AD.

Age Factors↗
PubMed1990

Alterations in in situ prolactin secretory granule morphology and immunoactivity by thiols and divalent cations.

The mechanisms involved in PRL storage in secretory granules are generally poorly understood. Recent studies with isolated granules, however, have suggested that granule storage forms may be relatively osmotically inactive due to oligomerization involving hormonal intermolecular disulfide bonds. Thus, expenditure of metabolic energy by the cell in order to maintain granule integrity would be reduced. When secretion is stimulated, oligomer depolymerization by thiol exchange mechanisms has been proposed to occur before or even concomitant with exocytosis. The present studies were designed to investigate the influence of metabolic inhibitors, thiols, and divalent cations on PRL storage in situ, rather than in isolated granules. The results suggest that 1) PRL granules require little energy to maintain their structure, since a combination of azide (10 mM), fluoride (10 mM), and cyanide (1 mM) had no effect on PRL granule morphology in normal anterior pituitary cells in primary culture; 2) disulfide linkages are involved in the osmotic activity of the PRL granule contents, since thiols induced granule swelling in lightly fixed cells; and 3) thiols and divalent cations are capable of altering the arrangement of stored hormone molecules, since PRL immunoactivity could be modified by these agents in glycol methacrylate-embedded exposed granule cores.

Animals↗
PubMed1985

Comparison of the ocular effects of atropine or glycopyrrolate with two I.V. induction agents.

Atropine and glycopyrrolate combined with either methohexitone or thiopentone were compared with the induction agent alone in patients undergoing electroconvulsive therapy. Patients acted as their own controls in each sub-group defined by induction agent. Pupil size, muscle twitches, presence of hiccups and the extent of oropharyngeal secretions were noted. Methohexitone produced a greater and more prolonged increase in pupil size than did thiopentone. The subsequent pupil size following the atropine-methohexitone mixture was significantly greater than that following the glycopyrrolate-methohexitone mixture. The combination of atropine with thiopentone produced a greater "secondary" mydriasis than thiopentone alone, or thiopentone combined with glycopyrrolate. The effect of the glycopyrrolate-thiopentone combination did not differ significantly from that of thiopentone alone. Methohexitone was associated with a greater incidence of hiccups, muscle twitching and excessive salivation.

Adult↗
PubMed1984

Cardiac dysrhythmias and heart rate changes at induction of anaesthesia: a comparison of two intravenous anticholinergics.

Glycopyrrolate, 0.2 mg, or atropine, 0.6 mg, was administered intravenously together with methohexitone for the induction of anaesthesia in unpremedicated patients. The use of atropine, compared with glycopyrrolate, was associated with a greater rise in heart rate, a greater number of patients whose heart rates doubled, and a higher incidence of dysrhythmias. Glycopyrrolate is recommended for use as an intravenous anticholinergic agent, particularly in patients with cardiovascular impairment.

Adolescent↗
PubMed1983

Intravenous glycopyrrolate and atropine at induction of anaesthesia: a comparison.

In unpremedicated patients presenting for general anaesthesia for electroconvulsive therapy (ECT), the use of atropine combined with methohexitone as an intravenous induction agent was found to produce a significantly greater increase in heart rate than glycopyrrolate in similar combination. There was no difference in the antisialogogue effect of the two drugs at the doses used, and both drugs provided similar protection against the effects of suxamethonium and ECT on heart rate.

Anesthesia, General↗
PubMed1981

Ventilatory capacity after three methods of anaesthesia for inguinal hernia repair: a randomized controlled trial.

One hundred consecutive male patients undergoing elective inguinal herniorrhaphy were randomized to receive general, epidural or local anaesthesia, and the patterns of ventilation were studied before and after operation. General anaesthesia caused more depression of FEV1 and FVC than the other two methods, but no important arterial hypoxia or clinical chest complications ensued. One patients suffered minor staphylococcal wound infection, and one died of massive pulmonary embolism on the eleventh day.

Adult↗
PubMedDate not supplied

Transgenic mice expressing APP-C100 in the brain.

The classic hallmarks of Alzheimer's disease are the deposition of amyloid in plaques and in the cerebrovasculature, and the emergence of neurofibrillary tangles in neurons. The interplay between these two pathologic processes, on the one hand, and the degeneration of neurons and loss of cognitive functions on the other, remains incompletely understood. We have proposed that one crucial component of this interplay is a fragment of the Alzheimer amyloid protein precursor (APP) comprising the carboxyterminal 100 amino acids of this molecule, which we term APP-C100 (or, more simply, C100). This fragment, which comprises the 42-amino acid amyloid protein (A beta) and an additional 58 amino acids carboxyterminal to it, was found to be toxic specifically to nerve cells in vitro. We developed transgenic mouse models to test the hypothesis that APP-C100 causes Alzheimer's disease neuropathology. APP-C100 was delivered to the mouse brain via a transgene expressing C100 under the control of the dystrophin brain promoter. These transgenic animal models for the action of APP-C100 in the brain exhibited some of the neuropathological features characteristic of Alzheimer disease brain. The animal models that we have created can be used to test hypotheses concerning the mechanism by which C100 interacts with a neuronal receptor to kill neurons.

Alzheimer Disease↗