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Biomedical subjects

R Mooney

Publications and source records attributed to R Mooney.

At least 37 records · Page 2Linked to original sources

The effects of cadmium exposure on the cytology and function of primary cultures from rainbow trout.

Cultured epidermal cells from explants of skin of rainbow trout were used to study the cytological and functional changes following sublethal exposure to cadmium stress. The aim was to develop diagnostic markers for ecotoxicology. Cultures were exposed to the pollutant for 48 h. Cell structural and cytological changes were established by light and electron microscopy. Metabolic alterations were detected by immunohistochemistry. The relation between the initiation of cellular alterations and cadmium concentrations was compared in cultures exposed in commercially-available serum-free and serum-containing medium. The expression of stress proteins (metallothionein and heat shock protein) was also studied. Rainbow trout epithelial cells exposed to cadmium showed typical morphological changes indicative of cell death by apoptosis. Sublethal exposure also resulted in cellular metabolic disturbances with increased deposits of glycogen. Increased melanization was also observed. These changes appeared at lower concentrations of cadmium when cells were exposed in serum-free media than in serum-containing media. Cadmium induced the expression of heat shock proteins but not of metallothioneins. The results broadly confirm in vivo findings for cadmium toxicity and suggest that this in vitro technique may have applications in aquatic toxicology.

Animals↗

Expression of delayed toxicity and lethal mutations in the progeny of human cells surviving exposure to radiation and other environmental mutagens.

PURPOSE: Delayed expression of lethal mutations in the progeny of cells which survived a toxic insult was first shown for ionizing radiation and is one of the signs of induced genomic instability. The effect appears to be related to DNA strand breakage or repair but not to the physical break itself. To investigate this and the relationship of lethal mutations or delayed death to other instability endpoints, cultures of immortal but non-transformed human keratinocytes were exposed to a range of environmental mutagens or cytotoxic compounds with different DNA damaging properties. METHODS: Delayed expression of damage was assessed by scoring a number of endpoints in the progeny of cells which survived exposure and underwent at least 15 population doublings. Endpoints included delayed apoptosis, cloning efficiency of cells in 'healthy' colonies and expression of the apoptosis regulatory proteins bcl-2 and BAX. RESULTS: The results clearly linked expression of delayed lethal mutations with substances that induced DNA strand breaks. All these substances are known also to induce oxidative stress. The occurrence of delayed damage required a threshold level of toxicity in the initially exposed population, which was remarkably similar for all the effective substances except cadmium. Alkylating agents or microtubule poisons that do not permit repair of DNA damage did not cause any delayed death. CONCLUSION: It is concluded that delayed cell death may be caused by widespread radical damage to DNA which is either signalled, thereby inducing an apoptotic response, or (mis-)repaired yielding a weak or unstable genome. It is likely that the process may be an important factor in determining the long-term response of populations to 'sublethal' levels of environmental mutagens whose mechanism of action includes DNA strand breakage and repair.

Antineoplastic Agents↗

Dose reduction in a paediatric X-ray department following optimization of radiographic technique.

A survey of radiation doses to children from diagnostic radiography has been carried out in a dedicated paediatric X-ray room. Entrance surface dose (ESD) and dose-area product (DAP) per radiograph were simultaneously measured with thermoluminescent dosemeters (TLDs) and a DAP meter to provide mean dose values for separate age ranges. Results of ESD and DAP were lower than the mean values from other UK studies for all ages and radiographs, except for the infant pelvis AP radiograph. Comparison of ESD and radiographic technique with CEC quality criteria highlighted a need for reduction of dose to infants and implied an increase in tube filtration might overcome the limitations of the room's three-phase, 12-pulse generator, allowing higher tube potentials to be used on infants. Additional tube filtration of 3 mmA1 was installed following assessment of dose reduction and image quality with test objects and phantoms, and confirmation from the paediatric radiologist that clinical image quality was not-significantly altered. The tube potential was increased from 50 to 56 kVp for the infant pelvis AP radiograph. The resulting ESD and effective dose fell by 51% and 38%, respectively. The CEC quality criteria have proved useful as a benchmark against which technique in X-ray departments can be compared, and as such are a useful tool for optimizing radiographic technique and reducing patient dose.

Adolescent↗

Development of intrinsic and synaptic properties in a forebrain nucleus essential to avian song learning.

In male zebra finches, the lateral magnocellular nucleus of the anterior neostriatum (LMAN) is necessary for the development of learned song but is not required for the production of acoustically stereotyped (crystallized) adult song. One hypothesis is that the physiological properties of LMAN neurons change over development and thus limit the ability of LMAN to affect song. To test this idea, we used in vitro intracellular recordings to characterize the intrinsic and synaptic properties of LMAN neurons in fledgling [posthatch days (PHD) 22-32] and juvenile zebra finches (PHD 40-51) when LMAN lesions disrupt normal song development, and in adults (>PHD 90) when LMAN lesions are without effect. In fledglings, depolarizing currents caused LMAN projection neurons to fire bursts of action potentials because of a putative low-threshold calcium spike (LTS). In contrast, juvenile and adult LMAN projection neurons fired accommodating trains of action potentials when depolarized but did not exhibit the burst mode of firing. Electrical stimulation of thalamic afferents elicited both monosynaptic EPSPs mediated by AMPA and NMDA receptors and polysynaptic IPSPs mediated by GABAA receptors from LMAN neurons at all ages studied here. In whole-cell voltage-clamp recordings, the EPSCs (NMDA-EPSCs) consisted of fast and slow components. Unlike juvenile and adult NMDA-EPSCs, those in fledglings were dominated by the slower component. Thus, both the intrinsic and synaptic properties of LMAN neurons change markedly during early song development (PHD 22-40) and achieve several adult-like properties during early sensorimotor learning and well before the time when LMAN lesions no longer disrupt song development.

2-Amino-5-phosphonovalerate↗

Tethering of the large subunits of Escherichia coli RNA polymerase.

The rpoB and rpoC genes of eubacteria and archaea, coding, respectively, for the beta and beta'-like subunits of DNA-dependent RNA polymerase, are organized in an operon with rpoB always preceding rpoC. Here, we show that in Escherichia coli the two genes can be fused and that the resulting 2751-amino acid beta::beta' fusion polypeptide assembles into functional RNA polymerase in vivo and in vitro. The results establish that the C terminus of the beta subunit and the N terminus of the beta' subunit are in close proximity to each other on the surface of the assembled RNA polymerase during all phases of the transcription cycle and also suggest that RNA polymerase assembly in vivo may occur co-translationally.

DNA-Directed RNA Polymerases↗

Bird song: of tone and tempo in the telencephalon.

Songbirds learn a new song by matching the sound they produce to a memorized model. A distributed central pattern-generating circuit has now been identified that governs song production; the new results have important implications for the way songs are learned.

Animals↗

Thalamic relay of spontaneous retinal activity prior to vision.

Before vision, retinal ganglion cells produce spontaneous waves of action potentials. A crucial question is whether this spontaneous activity is transmitted to lateral geniculate nucleus (LGN) neurons. Using a novel in vitro preparation, we report that LGN neurons receive periodic barrages of postsynaptic currents from the retina that drive them to fire bursts of action potentials. Groups of LGN neurons are highly correlated in their firing. Experiments in wild-type and NMDAR1 knockout mice show that NMDA receptor activation is not necessary for firing. The transmission of the highly correlated retinal activity to the LGN supports the hypothesis that retinal waves drive retinogeniculate synaptic remodeling. Because LGN neurons are driven to fire action potentials, this spontaneous activity could also act more centrally to influence synaptic modification within the developing visual cortex.

2-Amino-5-phosphonovalerate↗

Waiting periods versus early innervation: the development of axonal connections in the zebra finch song system.

This study examines the development of two neural pathways within the zebra finch forebrain that function respectively in the juvenile acquisition and the adult production of learned song. In the adult male zebra finch forebrain, the song nuclei L-MAN and HVc both innervate nucleus RA; L-MAN plays a crucial role in juvenile song acquisition but, unlike HVc and RA, is not essential for adult song production. Previous studies have shown that HVc axons arrive at the dorsal border of RA as early as posthatch day 15 (day 15), and only enter the male RA after days 25-30, but never enter the female RA. The present study examines the development of axonal projections from L-MAN to RA and finds that, in contrast to HVc axons, L-MAN terminals are present within the male and female RA by day 15, and persist there throughout adult life. Unlike RA-projecting HVc neurons, HVc neurons projecting to area X innervate this target by day 20. Like L-MAN, area X plays a transient role in song acquisition. These results suggest that in the zebra finch forebrain, neural pathways essential to juvenile song learning develop before those needed for adult song production.

Animals↗

Enhancement of transmission at the developing retinogeniculate synapse.

Axon terminals from retinal ganglion cells in the left and right eyes initially overlap with each other in the lateral geniculate nucleus of the neonatal ferret, then segregate into eye-specific layers via an activity-dependent process. Brain slices were used to show that, during this period of reorganization, retinal terminals within the lateral geniculate nucleus evoke excitatory postsynaptic currents composed of both NMDA and non-NMDA receptor-mediated currents. The amplitude of these currents could be enhanced for several tens of minutes to more than an hour by several bursts of high frequency synaptic stimulation, and the induction of enhancement appears to depend on NMDA receptor activation. Synaptic enhancement such as this could provide one of the physiological mechanisms by which retinal terminals segregate into eye-specific layers during development.

Animals↗

Graded pelvic muscle exercise. Effect on stress urinary incontinence.

The purpose of this research was to determine the effect of pelvic muscle exercise (PME) on stress urinary incontinence in middle-aged and elderly women. The protocol required 16 weeks of exercise three times per week, for a total of 48 sessions. Measures were taken at baseline, after a 4-week control period and after 4, 8, 12 and 16 weeks of PME, corresponding to PME levels 1, 2, 3 and 4, respectively. Urine loss was evaluated using a urinary diary and 24-hour pad test at baseline, after the control period and after PME levels 2 and 4. Pelvic muscle function was evaluated every four weeks. Sixty-five parous women 35-75 years of age (mean, 51.3) with mild to moderate stress urinary incontinence were studied. No significant changes in the outcome variables were found after the control period. The results showed significant reductions in urine loss on the 24-hour pad test (t = -4.7, P < or = .0001), and episodes of urine loss decreased from 2.6 to 1.0 between the control period and PME level 4. In addition, a significant improvement occurred in pressures developed by the pelvic muscles in response to PME (t = 6.8, P < or = .0001). Significant correlations between changes in pelvic muscle pressure and in urine loss variables were not found. Women who completed the study experienced a significant reduction in the amount of urine loss as well as a significant increase in pelvic muscle characteristics.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Synaptic basis for developmental plasticity in a birdsong nucleus.

The development and adult production of birdsong are subserved by specialized brain nuclei, including the robust nucleus of the archistriatum (RA), and its afferents originating in the caudal nucleus of the ventral hyperstriatum (HVc) and the lateral portion of the magnocellular nucleus of the anterior neostriatum (L-MAN). An in vitro brain slice preparation was used to characterize the electrophysiological properties of L-MAN and HVc axonal synapses within RA and to examine how these synaptic connections change during the course of song development. Electrical stimulation of L-MAN and not HVc fibers evoked excitatory synaptic potentials from virtually all RA neurons in brain slices prepared from male and female zebra finches less than 25 d of age. These "L-MAN" EPSPs were blocked substantially by the NMDA receptor antagonist D(-)-2-amino-5-phosphonopentanoic acid (D-APV; 50-100 microM) and by hyperpolarization of the postsynaptic membrane. In contrast, when slices were prepared from male finches greater than 35 d of age, electrical stimulation of the L-MAN and the HVc fiber tracts evoked synaptic responses from over 70% of RA neurons. Although the L-MAN EPSPs resembled those seen in RA before day 25, the "HVc" EPSPs were relatively insensitive to D-APV, but almost completely abolished by 6-cyano-7-nitroquinoxaline-2,3-dione, a non-NMDA glutamate receptor antagonist. These experiments indicate that L-MAN and HVc axons make pharmacologically distinct synapses on the same RA neurons, and that these synapses first form at different stages during development.

2-Amino-5-phosphonovalerate↗

Two distinct inputs to an avian song nucleus activate different glutamate receptor subtypes on individual neurons.

Although neural circuits mediating various simple behaviors have been delineated, those generating more complex behaviors are less well described. The discrete structure of avian song control nuclei promises that circuits controlling complex behaviors, such as birdsong, can also be understood. To this end, we developed an in vitro brain slice preparation containing the robust nucleus of the archistriatum (RA), a forebrain song control nucleus, and its inputs from two other song nuclei, the caudal nucleus of the ventral hyperstriatum (HVc) and the lateral part of the magnocellular nucleus of the anterior neostriatum (L-MAN). Using intracellular recordings, we examined the pharmacological properties of the synapses made on RA neurons by L-MAN and HVc axons. Electrical stimulation of the L-MAN and the HVc fiber tracts evoked excitatory postsynaptic potentials (EPSPs) from >70% of RA neurons when slices were prepared from male birds of 40-90 days of age, suggesting that many individual RA neurons receive excitatory input from L-MAN and HVc axons. The "L-MAN" EPSPs were blocked by the N-methyl-D-aspartate (NMDA) receptor antagonist D-(-)-2-amino-5-phosphonovaleric acid (D-APV) as well as the broad-spectrum glutamate receptor antagonist kynurenic acid but were relatively unaffected by the non-NMDA receptor blocker 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). In contrast, "HVc" EP-SPs were relatively insensitive to D-APV but almost completely abolished by CNQX. These experiments suggest that L-MAN and HVc axons provide pharmacologically distinct types of excitatory input to many of the same RA neurons.

Journal Article↗

Strength and function in the normal and rheumatoid hand.

We have reevaluated the Martin vigorimeter to measure grip strength in healthy subjects, and patients with rheumatoid arthritis (RA), and investigated the correlation of grip strength and hand function using the Jebsen hand function tests and Purdue pegboard test before and after treatment. The vigorimeter showed good test-retest reliability (r greater than 0.911) and interrater reliability (r greater than 0.915). Test-retest reliability was greater than 0.97 for the Jebsen test, and greater than 0.94 for the Purdue test in healthy individuals. Seventeen patients with RA were studied at intervals of 1 to 16 weeks. Active joint count and grip strength both improved significantly. Improvement in grip strength correlated with improvement in active joint count. Hand function tests were significantly impaired in the patients with RA.

Adolescent↗

Conventional and right precordial ECGs, creatine kinase, and radionuclide angiography in post-traumatic ventricular dysfunction.

Right ventricular infarction due to ischemic heart disease can be diagnosed by a right precordial electrogram or by first-pass radionuclide angiography (FPRNA). Prior FPRNA studies have shown that cardiac dysfunction after blunt chest trauma (myocardial contusion) is most often due to right ventricular dysfunction. We hypothesized that right ventricular dysfunction due to ischemic heart disease and myocardial contusion should produce similar ECG changes due to myocyte disruption. The purpose of our study was to evaluate the diagnostic value of the right precordial electrogram in suspected cardiac contusion. Thirty-five patients with suspected myocardial contusion based on mechanism of injury/clinical findings and no history of clinical heart disease were enrolled prospectively. All patients had conventional ECG, right precordial electrogram, and FPRNA studies. Twenty patients had normal cardiac scans (group 1); percentage of myocardial creatine kinase (CK-MB) was measured in 12 of these patients and was less than 5% in 11. Fifteen patients had abnormal cardiac scans (wall motion abnormality and/or decreased right ventricular ejection fraction) (mean, 34% +/- 7% [SD]; normal, greater than 40%) (group 2); percentage of CK-MB was measured in 13 of 15 patients and was less than 5% in all 13. Conventional ECGs and right precordial electrograms in all patients were analyzed for differences in heart rate, PR interval, QRS duration, corrected QT interval, and the axis of the frontal and horizontal plane QRS complex and ST segment. There were no significant differences between group 1 and group 2 patients. No patient with myocardial contusion diagnosed by FPRNA had elevated ST segments in V4R through V6R or a percentage CK-MB of more than 5%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Repetitive activity alters spike initiation locus and conduction velocity in Aplysia axons.

During a burst of spikes in the axon of neuron R2 of Aplysia, the spike initiation zone moves down the axon. The orthodromic latency of propagated spikes decreases as the trigger zone moves distally. At the same time, the conduction velocity of the spikes slows down, which leads to lengthening of interspike intervals, especially in remote regions of the axon. Similar timing changes are seen in the chemical and electrotonic postsynaptic potentials in some follower neurons of L10.

Action Potentials↗

Product of fetal crown-rump length and trunk area: ultrasound measurement in high-risk pregnancies.

Calculation of the product of crown-rump length and trunk area (CRL x TA), as measured by ultrasound between 34 and 36 weeks and combined with accurate assessment of gestational age in early pregnancy, was previously shown to be highly effective in detecting the small-for-dates fetus in a largely unselected series of patients. To assess the value of this two-stage schedule in high-risk pregnancies, 202 patients with singleton pregnancies at risk of fetal growth retardation were studied. Of the 53 babies that were small-for-dates at birth, 49 (92%) were identified in advance by CRL x TA measurement. In contrast to previous findings, measurement of trunk area (TA) alone was similarly effective, identifying in advance 48 (91%) of these small-for-dates babies.

Anthropometry↗