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Biomedical subjects

G Orr

Publications and source records attributed to G Orr.

At least 19 recordsLinked to original sources
PubMed2000

Chronic treatment of old rats with donepezil or galantamine: effects on memory, hippocampal plasticity and nicotinic receptors.

The function of the cholinergic system is known to change during normal aging and in pathological conditions such as Alzheimer's disease. The present study was designed to assess, within the same group of old animals, the behavioral, electrophysiological and neurochemical effects of chronic treatment with agents that increase the function of the cholinergic system through both muscarinic and nicotinic mechanisms. Doses were determined that produced 60% cholinesterase inhibition by donepezil and galantamine for the old rats. This was chosen to be analogous to therapeutic levels achieved for treatment of human Alzheimer's disease patients with these agents. Because of the well-known age-related changes in spatial memory and hippocampal synaptic plasticity, spatial working memory in the radial eight-arm maze and hippocampal long-term potentiation induction and decay, as well as nicotinic receptor density and affinity, were measured in old rats implanted with minipumps that delivered donepezil, galantamine or saline. There was no effect of drug treatment on baseline synaptic transmission or on the threshold or magnitude of long-term potentiation induction. Both drug treatment groups, however, showed significantly extended long-term potentiation decay times at the perforant path-granule cell synapse over the saline control animals, as measured during the week following induction. Both drugs also elevated the number of nicotinic receptors within the hippocampus and neocortex. This is the first demonstration of cholinergic modulation of synaptic plasticity over the time-course of days. Furthermore, the durability of long-term potentiation was significantly, positively correlated with nicotinic receptor binding in the hippocampus. Chronic treatment with donepezil or galantamine had no significant effect on a well-learned spatial working memory task on the radial maze. These data suggest that the therapeutic doses of cholinesterase inhibitors used to treat patients with Alzheimer's disease may have effects on neurophysiology and neurochemistry that are close to the threshold for producing detectable behavioral improvements.

Acetylcholinesterase↗
PubMed2000

Age-related decrease in the Schaffer collateral-evoked EPSP in awake, freely behaving rats.

Synaptic response size in the CA1 region of the hippocampus in aged rats is reduced for a given stimulus intensity, compared with that elicited in young rats. Consistent with the in vitro findings of reduced Schaffer collateral-evoked CA1 EPSPs in old rats, the population currents evoked to iontophoretically applied AMPA are also smaller relative to the presynaptic fiber potential amplitude. On the other hand, the size of the presynaptic fiber potential and amplitude of unitary intra-cellularly recorded EPSP responses do not change across age in the CA1 region. These electrophysiological findings are consistent with the hypothesis that old rats have fewer functional synaptic contacts per Schaffer collateral axon than do young rats. The possibility that this age change arises as a result of a differential tissue recovery response to in vitro preparation was examined in the present study. CA1 presynaptic fiber potential and EPSP amplitudes evoked by the stimulation of Schaffer collateral afferents were studied in intact, freely behaving young and old rats. We confirmed in vivo the pattern of electrophysiophysiological results previously reported in vitro and found significant correlations between the synaptic response amplitudes and the accuracy of spatial behavior in the Morris swim task. The data suggest that changes in functional connectivity of old rats may be a significant contributor to cognitive changes during aging.

Afferent Pathways↗
PubMed2000

Cushing's syndrome presenting as a schizophrenia-like psychotic state.

Neuropsychiatric abnormalities, of which depression is the most common, are frequently associated with Cushing's syndrome. The following paper describes a 58-year-old woman in whom a prolonged psychotic state--schizophrenia-like--was the presenting sign of Cushing's syndrome. The psychiatric symptoms disappeared shortly after the cortisol level has been normalized. Due to the variety of symptoms, both organic and psychiatric, which may occur with Cushing's syndrome, a high suspicion index is advisable. Suspect clinical findings should always prompt the appropriate endocrine work-up.

Cushing Syndrome↗
PubMed1995

Prospective, randomised, controlled trial comparing suture needle drainage and argon laser drainage of subretinal fluid.

AIMS: This study was designed to compare suture needle drainage (SND) with argon laser drainage (ALD) of subretinal fluid. METHODS: A prospective, randomised, controlled, clinical trial was carried out on 93 patients undergoing external drainage of subretinal fluid during scleral buckling surgery for rhegmatogenous retinal detachment. The incidence of successful drainage, incidence of subretinal haemorrhage, incidence of retinal incarceration, and incidence of retinal perforation were determined. RESULTS: The success rate was 97.9% in the ALD group and 84.8% in the SND group (difference-13.1%, 95% CI-26.4% to 2.0%). The incidence of clinically significant subretinal haemorrhage was 4.3% in the ALD group compared with 28.3% in the SND group (difference 24.0%, 95% CI 7.6% to 40.4%). The incidence of incarceration was comparable in each group. There were no cases of retinal perforation. CONCLUSIONS: The use of ALD was associated with a higher rate of successful SRF drainage, and a lower incidence of clinically significant subretinal haemorrhage than SND. ALD is preferred when an endolaser is available.

Adolescent↗
PubMed1994

Peach (Prunus persica) endopolygalacturonase cDNA isolation and mRNA analysis in melting and nonmelting peach cultivars.

Two distinct partial cDNAs, PRF1 and PRF3, similar in sequence to previously described polygalacturonases, were amplified from ripe peach (Prunus persica L. Batsch cv Flavorcrest) fruit cDNA by the polymerase chain reaction. PRF1-related RNA was present in fruit from early ripening at levels not detected by northern analysis. PRF3-related RNA was readily detectable in ripe fruit by northern analysis. PRF3 was used to isolate a cDNA with a complete open reading frame, PRF5, from a lambda ZAP II cDNA library prepared from poly(A)+ RNA of ripe peach fruit. PRF5 coded for a predicted protein of 393 amino acids with a molecular mass of 41,500 D. The derived amino acid sequence of PRF5 included a putative leader sequence of 23 amino acids, followed by a sequence that matched the N terminus of endopolygalacturonase protein purified from ripe peach fruit. By northern analysis, PRF3-related RNA was undetectable in firm, unripe Flavorcrest fruit. It appeared at low levels as a 1.7-kb transcript in fruit that had begun to ripen and soften and was very abundant in ripe fruit that had undergone the "melting" stage of softening. The marked increase in PRF3-related RNA levels took place over a period of less than 2 d at 20 degrees C and coincided with the climacteric peak in ethylene evolution. Levels of 1-aminocyclopropane-1-carboxylate oxidase-related RNA increased during ripening at a much earlier stage than levels of PRF3-related RNA. Lower levels of 1.7-kb RNA transcript were detected by PRF3 in ripe fruit of the melting cultivar Fragar, which are firmer than Flavorcrest fruit. In ripe fruit of the nonmelting cultivar Carolyn, PRF3 detected a 1.45-kb RNA transcript that was present at low levels. Transcripts of a peach polygalacturonase-related genomic sequence were not detected in ripening fruit.

Amino Acid Sequence↗
PubMed1993

Trans-scleral fixation of dislocated posterior chamber intraocular lenses using a 9/0 microsurgical polypropylene snare.

We describe a new technique for retrieval, sulcus relocation and trans-scleral fixation of posteriorly dislocated (posterior chamber intraocular lenses (PC-IOLs) in a closed eye using a 9/0 polypropylene snare instrument adapted specifically for this purpose. Our experience is described of the first 5 consecutive cases in which the snare was used. The posteriorly dislocated PC-IOL was successfully relocated in 4 of these cases but per-operative fracture of a lens haptic necessitated removal of the IOL in the fifth. A number of surgical techniques have already been described in the management of this problem but we consider the polypropylene snare to offer the advantages of a simpler technique that obviates the need for either manipulation of needles within the eye or complex suturing procedures.

Adult↗
PubMed1992

Thrombospondin as a component of the extracellular matrix of epiretinal membranes: comparisons with cellular fibronectin.

We compared the distribution of the adhesive extracellular matrix glycoproteins thrombospondin and cellular fibronectin in epiretinal membranes. A total of nine membranes were investigated with immunohistochemical techniques. Thrombospondin and cellular fibronectin immunoreactivity were observed in seven of the specimens and immunostaining for the two glycoproteins was co-localised in four of the membranes. The findings indicate that thrombospondin contributes to the extracellular glycoprotein content of epiretinal membranes and is frequently co-distributed with cellular fibronectin in the tissue. As a consequence, thrombospondin may play a role in the assembly of the extracellular matrix of epiretinal membranes.

Diabetic Retinopathy↗
PubMed1992

Four-quadrant local anaesthesia technique for vitreoretinal surgery.

We report our experience of a recently described local anaesthetic technique which seeks to avoid risk of perforation of the globe, damage to the optic nerve, or injection into the subarachnoid space, whilst providing prolonged and reliable anaesthesia. A prospective series of 19 patients who underwent vitreoretinal surgery using this technique were compared with 19 patients who had retrobulbar anaesthesia for cataract extraction. The vitreoretinal group had excellent akinesia and very good anaesthesia, allowing prolonged retinal reattachment surgery lasting up to 3 hours. Patient evaluation of discomfort or pain experienced in the two groups was assessed using a visual analogue pain score chart. The pain scores for the two groups were not significantly different (p = 0.03) and 16 of 19 patients in each group (84%) experienced only slight pain or less. Satisfaction with local anaesthesia, in both groups, was also assessed by asking patients which method of anaesthesia they would prefer if future surgery were to be performed. In the vitreoretinal group, 18 of 19 patients expressed a preference for local anaesthesia and in the cataract group 17 ot 19 also favoured local anaesthesia. The vitreoretinal patients' median pain score was 0 compared with 1 for the cataract patients. This study demonstrates that local anaesthesia provides pain relief for vitreoretinal surgery which is comparable to the experience of patients undergoing cataract surgery by retrobulbar anaesthesia. The technique described can provide successful local anaesthesia for vitreoretinal procedures. The success of this technique for pain relief and akinesia calls for a reappraisal of the number of patients suitable for vitreoretinal surgery under local anaesthesia.

Anesthesia, Local↗
PubMed1992

Determinants of bone density in young women. I. Relationships among pubertal development, total body bone mass, and total body bone density in premenarchal females.

Bone mass accretion during puberty appears to be critical in the development of peak bone mass, which, in turn, is believed to be a major determinant of osteoporosis risk. Although genetics may be the primary determinant of peak bone mass, modifiable secondary factors, such as nutrition and hormone exposure, may significantly affect bone mass accretion during the second decade of life. As part of a longitudinal study of major determinants of bone development during puberty, we obtained cross-sectional measurements from 112 premenarchal caucasian females (mean +/- SD age, 11.9 +/- 0.49 yr at study entry). Total body bone mineral density (TBBMD) and total body bone mineral content (TBBMC) were measured by dual energy x-ray absorptiometry and compared to anthropometric, pubertal development, urinary steroid and gonadotropin levels, and nutrient intake. An integrated estrogen exposure index was developed and used to evaluate the cumulative effect of circulating estrogen levels on both development. Compared to normative reference data for adults, our subjects possessed 90% of adult height, 68% of adult weight, 83% of adult TBBMD, and 53% of TBBMC. The strongest combined predictors of prepubertal TBBMD and TBBMC were body weight, followed by height and pubertal development. Urinary estradiol levels were positively correlated with dietary intake of iron and vitamin B6.

Adolescent↗
PubMed1990

Purification and characterization of fatty acid beta-oxidation enzymes from Caulobacter crescentus.

Acetoacetyl coenzyme A (acetoacetyl-CoA) thiolase, an enzyme required for short-chain fatty acid degradation, has been purified to near homogeneity from Caulobacter crescentus. The relative heat stability of this enzyme allowed it to be separated from beta-ketoacyl-CoA thiolase. The purification scheme minus the heating step also permitted the copurification of crotonase and 3-hydroxyacyl-CoA dehydrogenase. These activities are in a multienzyme complex in Escherichia coli, but a similar complex was not observed in C. crescentus. Instead, separate proteins differing in enzymatic activity were detected, analogous to the beta-oxidation enzymes that have been isolated from Clostridium acetobutylicum and from mitochondria of higher eucaryotes. In these cells, as appears to be the case with C. crescentus, the individual enzymes form multimers of identical subunits.

3-Hydroxyacyl CoA Dehydrogenases↗
PubMed1990

Construction of a protoglomerular template by olfactory axons initiates the formation of olfactory glomeruli in the insect brain.

Olfactory glomeruli in insects share many features of organization with their vertebrate counterparts, and yet offer distinct advantages for study of neuronal development. Previous studies have revealed that the olfactory lobes of the brain of the moth Manduca sexta arise postembryonically and that glomeruli in the lobe are induced by olfactory afferent axons (Hildebrand et al., 1979; Oland and Tolbert, 1987). In the present study, we have used the Golgi method, intracellular labeling of neurons with Lucifer yellow, and electron microscopy to follow neuronal development in the antennal lobe through the period when glomeruli develop. Our results, taken together with other results from our laboratory, suggest that olfactory sensory axons have the intrinsic ability to form protoglomeruli, and that an interaction between these axons and glial cells (but not the majority of the neurons of the antennal lobe) causes the glial cells to surround the protoglomeruli. Ingrowth of the neurites of most antennal-lobe neurons into the protoglomeruli occurs after a small delay and appears to be constrained to glomerular units by the presence of the glial boundaries. Synapses, initially not detected in the protoglomeruli, begin to appear as soon as the neurites of antennal-lobe neurons appear in the glomeruli. Thus, antennal axons, instead of immediately seeking out postsynaptic targets, first form the template for organization of future glomeruli. The neurites of most of the neurons of the antennal lobe grow outward to meet the olfactory sensory axons, and in doing so, join with these axons to form glomeruli. Preliminary results concerning the development of a second class of neuron in the lobe, the projection neurons, indicate that at least some of these neurons may arborize in the region of the protoglomeruli very early and therefore participate with the afferent axons in laying the foundation for glomeruli.

Afferent Pathways↗
PubMed1988

Calmodulin supports the force-generating function in desensitized muscle fibers.

Externally added calmodulin (CaM) restored Ca2+ regulation for the tension development by skeletal muscle fibers of hamster and rabbit desensitized by the troponin C (TnC) extraction treatment. CaM produced this action by combining with the TnC-denuded sites in the fiber. However, the binding properties differed strikingly from TnC: unlike TnC, CaM binding required the continued presence of Ca2+ and the bound portion was completely released with EGTA in the physiological milieu. The maximal uptake was 1.7 g of CaM/kg of muscle in the present study. The apparent Ca2+ sensitivity for force development with 200 micrograms/ml CaM in the solution was lower than in the native fiber or in the TnC-loaded fiber. The apparent association constant for CaM binding to the TnC-denuded sites was found as 4.9 x 10(5) M-1, and the extrapolated maximum force (Fmax) with CaM was close to PO. The intrinsic CaM level in intact muscle was also measured and was 18.6 mg/kg, amounting to about 1% of the total TnC or the CaM uptake by TnC-denuded fibers. The intrinsic CaM was not dislodged by EDTA treatment, indicating tight binding and suggesting that it exists in a separate pool from the vacated TnC sites adsorbing externally added CaM. The stringent Ca+ dependence of the CaM adsorption to TnC sites in the regulatory complex in the fiber supports the view that the evolutionary replacement of residues in the amino terminus helix portion of the "EF-hand" motif of site IV may be critical for the functional specialization by TnC.

Animals↗
PubMed1987

Morphologic observations on experimental subretinal neovascularization in the monkey.

Subretinal neovascularization is a poorly understood and potentially disastrous feature of many eye diseases. We used light and electron microscopy to study the sequence of events that lead to the formation of new vessels after laser photocoagulation of the retina and choroid of primates. In this animal model there is a rapid development of new blood vessels; one day after photocoagulation, endothelial cell degeneration and thrombus formation were observed in the capillaries, venules and arterioles of the choroid around the center of the lesion. Re-endothelialization began in some thrombosed choroidal vessels, with migration of the activated endothelial cells within the old basement membrane. Two days after photocoagulation, re-endothelialization was observed in almost all thrombosed choroidal vessels, and the initial stage of the endothelial cell budding was observed in the pre-existing choroidal vessels; this was especially prominent in venules with pericytes. Three days after photocoagulation, not only the endothelial cells in pre-existing vessels but also those in re-endothelialized vessels showed budding and lumen formation. The lumen of vessels was formed by the budding of adjacent endothelial cells that were coupled by transient intercellular junctions. Mitotic figures were frequently found in the endothelial cells distal to the growing tip. Five to eight days after photocoagulation, many new vessels extended into the subretinal space.

Animals↗
PubMed1986

Aqueous concentrations of fluorouracil after intravitreal injection. Normal, vitrectomized, and silicone-filled eyes.

Treatment of postoperative vitreoretinopathy with combined intravitreal fluorouracil and liquid silicone may result in increased corneal and retinal toxicity. We therefore investigated the movement of carbon 14-labeled fluorouracil from the vitreous into the anterior chamber in normal rabbit eyes and in eyes filled with either balanced salt solution or silicone after vitrectomy and lensectomy, with or without preservation of the anterior capsule. Only 0.56% of intravitreally injected fluorouracil was recovered from the anterior chamber over a four-hour period in normal eyes. This impermeability was partly maintained if the anterior capsule was retained (9.98%), particularly if the eye contained silicone (2.52%). The greatest amount was recovered when both lens capsules were removed (43.7%). Corneal toxicity is most likely to occur in this situation.

Animals↗
PubMed1986

Relative permeability of retina and retinal pigment epithelium to the diffusion of tritiated water from vitreous to choroid.

The movement of intravitreally injected tritiated water from the vitreous to the choroid was accelerated by the removal of intervening retina. Both rate of transfer and peak choroidal levels of the tracer were increased, but the proportion of the intravitreal dose recovered was unaltered. In contrast, the movement of tritiated water after diffuse damage to the retinal pigment epithelium by sodium iodate was similar to that of control eyes. The main resistance to the diffusion of this tracer from the vitreous to the choroid is the retina. The differential permeability of the retina and the retinal pigment epithelium may have a role in normal retinal adhesion.

Animals↗