33 results on '"Kelly, S. S."'
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2. Ex vivo expansion of cord blood
- Author
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Kelly, S S, Sola, C B S, de Lima, M, and Shpall, E
- Published
- 2009
- Full Text
- View/download PDF
3. Fluorescent staining of living mouse neuromuscular junctions
- Author
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Kelly, S. S., Anis, N., and Robbins, N.
- Published
- 1985
- Full Text
- View/download PDF
4. The effects of age and nutritional state on m.e.p.p. amplitude
- Author
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Kelly, S. S.
- Published
- 1978
- Full Text
- View/download PDF
5. Peripheral placement of apheresis catheters in children: feasibility, safety, and efficacy in the collection of blood stem cells--initial experience.
- Author
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Harned RK 2nd, Kelly SS, Foreman NK, and Giller RH
- Subjects
- Adolescent, Adult, Child, Equipment Design, Feasibility Studies, Female, Follow-Up Studies, Humans, Male, Catheterization, Catheterization, Peripheral instrumentation, Catheterization, Peripheral methods, Hematopoietic Stem Cells, Leukapheresis
- Abstract
An 8-F 24-cm-long apheresis catheter was placed in the basilic vein with imaging-guided percutaneous technique in 15 children undergoing leukapheresis for collection of autologous peripheral blood stem cells. There were no immediate or long-term complications. This is a low-morbidity procedure requiring minimal sedation that results in successful collection of peripheral blood stem cells and allows flow rates comparable to those with surgically placed central catheters.
- Published
- 2001
- Full Text
- View/download PDF
6. A comparison of the electrophysiological effects of two organophosphates, mipafox and ecothiopate, on mouse limb muscles.
- Author
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de Blaquière GE, Williams FM, Blain PG, and Kelly SS
- Subjects
- Acetylcholinesterase analysis, Action Potentials drug effects, Animals, Cholinesterase Inhibitors administration & dosage, Echothiophate Iodide administration & dosage, Electric Stimulation, Hindlimb physiology, Injections, Subcutaneous, Isoflurophate administration & dosage, Isoflurophate toxicity, Male, Mice, Muscle, Skeletal enzymology, Cholinesterase Inhibitors toxicity, Echothiophate Iodide toxicity, Hindlimb drug effects, Isoflurophate analogs & derivatives, Muscle, Skeletal drug effects
- Abstract
Adult male albino mice were given single subcutaneous injections of either mipafox (110 mumol/kg) or ecothiopate (0.5 mumol/kg), two organophosphorus compounds (OPs). Acetylcholinesterase activity was measured in the soleus (slow-twitch) and extensor digitorum longus (EDL; fast-twitch) muscles. At 7 and 28 days after dosing, in vitro electrophysiological measurements were carried out in the soleus and EDL. Action potentials and end-plate potentials were evoked at 30 Hz and recorded intracellularly from single muscle fibers. The amplitudes, time course, and latencies of these potentials were measured and the variability (jitter) of latencies was calculated. Recordings after mipafox were also made with 3-Hz stimulation. Acetylcholinesterase activity was inhibited by mipafox (65% in the soleus; 76% in the EDL) and ecothiopate (59% in the soleus; 42% in the EDL). Mipafox and ecothiopate both increased postjunctional (muscle action potential) jitter in the soleus and EDL at 7 days after dosing. Organophosphates caused an increase in end-plate potential amplitudes in the soleus. Mipafox caused an increase in prejunctional (end-plate potential) jitter at 28 days after dosing in both muscles. A single dose of ecothiopate also caused an increase in prejunctional jitter at 28 days in the soleus. The OP-induced increase in jitter was different at different frequencies of stimulation. The results show that there are electrophysiological changes in both muscles after administration of organophosphorus compounds. The slow-twitch soleus appears more sensitive to prejunctional changes caused by OPs than the fast-twitch EDL.
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- 1998
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7. Isolation of a new okadaic acid analogue from phytoplankton implicated in diarrhetic shellfish poisoning.
- Author
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Draisci R, Giannetti L, Lucentini L, Marchiafava C, James KJ, Bishop AG, Healy BM, and Kelly SS
- Subjects
- Anthracenes chemistry, Chromatography, High Pressure Liquid methods, Fluorescent Dyes, Fluorometry, Mass Spectrometry, Okadaic Acid analysis, Pyrans analysis, Diarrhea chemically induced, Food Analysis, Foodborne Diseases, Marine Toxins analysis, Okadaic Acid analogs & derivatives, Phytoplankton chemistry
- Abstract
A new analogue of okadaic acid (OA), the toxin mainly responsible for diarrhetic shellfish-poisoning (DSP) phenomena in Europe, has been isolated from toxic phytoplankton (Dinophysis acuta) collected in Irish waters. Fluorimetric LC analyses of the extracts of bulk phytoplankton samples using derivatisation with 9-anthryldiazomethane (ADAM) showed a complex toxin profile, with peaks corresponding to OA and dinophysistoxin-2 (DTX-2) as well as a third unidentified compound. This minor unidentified component was isolated by chromatographic techniques such as normal-phase chromatography, gel permeation on Sephadex, solid-phase extraction and reversed-phase separations. Ionspray mass spectrometry (MS) was used for structural investigation on this compound due to the very small amount of isolated material. Flow injection analysis (FIA)-MS of the isolated compound gave positive-ion mass spectrum dominated by the protonated molecule, [M + H]+, at signal m/z 805, whereas the deprotonated molecule [M - H]- was observed in the negative-ion spectrum at signal m/z 803, thus indicating the molecular weight of 804 for the new toxin, the same as OA and its known isomers, DTX-2 and DTX-2B. Collision-induced dissociation (CID) as obtained by positive and negative tandem mass spectrometry (MS-MS) showed a fragmentation pattern for the new compound which was very similar to that of OA, DTX-2 and DTX-2B. Ionspray microLC-MS of a mixture containing the compound under investigation together with OA analogues showed the compound eluted after OA, DTX-2, DTX-2B and before DTX-1. All the chromatographic and mass spectrometric data indicated the compound to be another OA isomer and it was therefore coded DTX-2C. To the best of our knowledge this is the first report on the isolation of a new compound related to DSP toxins from natural communities of toxic phytoplankton.
- Published
- 1998
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8. Determination of diarrheic shellfish toxins in mussels by microliquid chromatography-tandem mass spectrometry.
- Author
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Draisci R, Lucentini L, Giannetti L, Boria P, James KJ, Furey A, Gillman M, and Kelly SS
- Subjects
- Animals, Chromatography, Liquid, Digestive System chemistry, Marine Toxins toxicity, Mass Spectrometry, Okadaic Acid analysis, Pyrans analysis, Solvents, Bivalvia chemistry, Diarrhea chemically induced, Marine Toxins analysis, Shellfish analysis
- Abstract
A fast, sensitive, and specific procedure for determining toxins that cause diarrheic shellfish poisoning (DSP) using microliquid chromatography coupled with tandem mass spectrometry (micro-LC-MS-MS) is reported. The lipophylic polyether acidic toxins okadaic acid (OA), its isomer dinophysistoxin-2 (DTX-2), the 35-methylokadaic acid dinophysistoxin-1 (DTX-1), and the novel toxin dinophysistoxin-1B (DTX-2B; recently isolated from Irish mussels) were extracted from shellfish tissues with acetone and chromatographed by isocratic elution at 10 microL/min with CH3 CN-H2O, 80 + 20 (v/v), containing 0.1% trifluoroacetic acid, through a C18 reversed-phase column (1.0 mm id). The chromatograph is coupled via an ion spray interface to an atmospheric pressure ionization source. Collision-induced-dissociation (CID) ion mass spectra of the protonated molecule, [M + H]+, at m/z 805 for OA, DTX-2, and DTX-2B and at m/z 819 for DTX-1, were obtained in MS-MS experiments to identify 2 diagnostic fragment ions for each analyte that could be used for selected-reaction-monitoring (SRM) micro-LC-MS-MS analysis. The CID spectrum of DTX-2B confirmed it to be a new OA isomer, like DTX-2. Standard curves obtained by SRM micro-LC-MS-MS were linear (r2 > or = 0.9992) over the range 0.05-1.00 micrograms/mL (i.e., 0.10-2.00 micrograms toxin/g hepatopancreas), and a detection limit of 15 pg/injection was obtained for each DSP toxin. Average recoveries ranged from 95 to 101%, and coefficients of variation ranged from 1.8 to 3.4%. This novel SRM micro-LC-MS-MS method was used to confirm acidic DSP toxins in Irish and Italian toxic mussels. It offers a high degree of specificity because analyte confirmation is based on retention time, molecular weight, structural information obtained from the presence of 2 diagnostic fragments for each analyte, and ion ratios. OA was found in both Irish (< or = 0.7 micrograms/g hepatopancreas) and Italian (< or = 1.5 micrograms/g hepatopancreas) mussels. DTX-1 was found only in Italian mussels (< or = 0.3 micrograms/g hepatopancreas). DTX-2 (< or = 6.1 micrograms/g hepatopancreas) and DTX-2B (< or = 0.08 micrograms/hepatopancreas) were unique to Irish shellfish.
- Published
- 1998
9. Identification of a new diarrhoetic toxin in shellfish using liquid chromatography with fluorimetric and mass spectrometric detection.
- Author
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James KJ, Carmody EP, Gillman M, Kelly SS, Draisci R, Lucentini L, and Giannetti L
- Subjects
- Animals, Bivalvia chemistry, Chromatography, High Pressure Liquid methods, Diarrhea chemically induced, Fluorometry, Marine Toxins analysis, Mass Spectrometry
- Abstract
A new toxin, dinophysistoxin-2B (DTX-2B) was isolated from Irish mussels using silica chromatography, gel permeation, octadecylsilane solid-phase extraction and repeated preparative high-performance liquid chromatography (HPLC). Dinophysistoxin-2 (DTX-2) was also isolated from shellfish using the same procedures. The separation of these toxins in chromatographic fractions was monitored using fluorimetric HPLC following derivatization with 9-anthrylmethyldiazomethane or 1-bromoacetylpyrene. Flow-injection analysis-mass spectrometry (FIA-MS) with an atmospheric pressure ionization (API) and an ionspray (ISP) interface showed a mass spectrum dominated by the protonated molecule, [M+H]+, at m/z 805 for DTX-2B, thus indicating that this new toxin has the same mol.wt as okadaic acid and DTX-2. The low-energy fragment ion spectrum, as produced in FIA-MS experiments by up-front collision-induced dissociation of the protonated molecule of DTX-2B, showed fragment ions corresponding to successive losses of water molecules from the [M+H]+ ion. This low collision energy fragmentation pattern is typical of marine polyether toxins such as okadaic acid, DTX-2 and DTX-1. These results provide strong evidence that DTX-2B is another okadaic acid isomer.
- Published
- 1997
- Full Text
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10. Effects of multiple doses of organophosphates on evoked potentials in mouse diaphragm.
- Author
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Kelly SS, de Blaquière GE, Williams FM, and Blain PG
- Subjects
- Action Potentials drug effects, Animals, Brain drug effects, Brain enzymology, Diaphragm physiology, Evoked Potentials drug effects, Isoflurophate administration & dosage, Male, Mice, Paraoxon administration & dosage, Cholinesterase Inhibitors administration & dosage, Diaphragm drug effects, Echothiophate Iodide administration & dosage, Insecticides administration & dosage, Isoflurophate analogs & derivatives
- Abstract
1. Male albino mice were injected s.c. with an organophosphate (mipafox, ecothiopate or paraoxon). Treatments were either a single injection or multiple daily injections with lower doses for 5 or 8 days. At 3 h after injection the activity of brain and diaphragm acetylcholinesterase and of brain neuropathy target esterase (NTE) was measured. Also measured in the diaphragm at 3 h post dose was the duration of spontaneous miniature endplate potentials (eMEPPs), recorded extracellularly. 2. At 7 and 28 days after dosing action potentials and evoked endplate potentials, produced by stimulating the phrenic nerve at 30 Hz, were recorded in diaphragm muscle. The amplitudes, time-course and latencies of these potentials were measured and the variability of latencies (jitter) was calculated. 3. Single doses of mipafox (20 mg/kg), ecothiopate (0.192 mg/kg) or paraoxon (0.415 mg/kg) in the mouse produced ca. 70% inhibition of diaphragm acetylcholinesterase at 3 h after dosing. All three OPs produced a prolongation of the half-decay times of eMEPPs. 4. All three OPs in the above single doses produced increased muscle action potential (postjunctional) jitter but only mipafox produced an increase in endplate potential (prejunctional) jitter. Mipafox in a slightly reduced single dose (17.5 mg/kg) had no effect on prejunctional or postjunctional jitter. 5. Multiple dosing with mipafox (8 mg/kg daily for 5 days) increased both postjunctional and prejunctional jitter at both 7 and 28 days after the end of dosing. After multiple dosing with mipafox (5 mg/kg daily for 5 days) postjunctional (but not prejunctional) jitter was increased. Multiple doses of paraoxon (0.166 mg/kg daily for 5 days) or ecothiopate (0.76 mg/kg daily for 5 days) increased prejunctional and postjunctional jitter. 6. Depending on the dosing regime, all three OPs tested were capable of increasing both prejunctional and postjunctional jitter. Neither ecothiopate nor paraoxon inhibited NTE, so this prejunctional effect is not likely to be related to 'classical' OP-induced delayed neuropathy. The prejunctional effects may be related to long-term inhibition of acetylcholinesterase and the triggering mechanism for increase in prejunctional jitter may involve a relationship between the inhibition of acetylcholinesterase and the time for which it is inhibited. The differences between the time-courses of increases in prejunctional and postjunctional jitter and the differential effects of the different multiple dosing regimes indicate that it is likely that the triggering relationship between enzyme inhibition and time is different for prejunctional and postjunctional effects.
- Published
- 1997
- Full Text
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11. The effects of multiple low doses of organophosphates on target enzymes in brain and diaphragm in the mouse.
- Author
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Williams FM, Charlton C, de Blaquière GE, Mutch E, Kelly SS, and Blain PG
- Subjects
- Animals, Brain enzymology, Diaphragm enzymology, Echothiophate Iodide pharmacology, Isoflurophate analogs & derivatives, Isoflurophate pharmacology, Male, Mice, Paraoxon pharmacology, Brain drug effects, Carboxylic Ester Hydrolases antagonists & inhibitors, Cholinesterase Inhibitors pharmacology, Diaphragm drug effects, Insecticides pharmacology
- Abstract
1. Multiple low doses of the direct acting organophosphates, ecothiopate, paraoxon and mipafox produced persistent and additive inhibition of diaphragm acetylcholinesterase. Paraoxon and mipafox had similar effects on brain acetylcholinesterase. There was greater recovery from inhibition between doses for paraoxon and ecothiopate than for mipafox. 2. Ecothiopate did not inhibit brain acetylcholinesterase but there was a small increase in activity. 3. Mipafox also had a cumulative inhibitory effect on brain neuropathy target esterase. 4. These results have particular implication for the use of multiple low doses of organophosphates occupationally by man.
- Published
- 1997
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12. Isolation of dinophysistoxin-2 and the high-performance liquid chromatographic analysis of diarrhetic shellfish toxins using derivatisation with 1-bromoacetylpyrene.
- Author
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Kelly SS, Bishop AG, Carmody EP, and James KJ
- Subjects
- Animals, Bivalvia chemistry, Indicators and Reagents, Okadaic Acid analogs & derivatives, Pyrenes, Reproducibility of Results, Spectrometry, Fluorescence, Chromatography, High Pressure Liquid methods, Dinoflagellida chemistry, Marine Toxins isolation & purification, Pyrans isolation & purification
- Abstract
The rare diarrhetic shellfish toxin, dinophysistoxin-2 (DTX-2), was isolated from the digestive glands of mussels (Mytilus edulis). This was achieved by chromatography on silica and Sephadex LH-20 followed by reversed-phase solid phase extraction and semi-preparative high-performance liquid chromatography (HPLC) with an Ultremex C18 column. Using 1-bromoacetylpyrene (BAP), as a precolumn derivatisation reagent, the diarrhetic shellfish toxins, okadaic acid (OA), dinophysistoxin-1 (DTX-1) and DTX-2, were determined by HPLC with fluorimetric detection. Derivatisation using BAP was compared with 9-anthryldiazomethane (ADAM) and, although the latter exhibited a four-fold better sensitivity, the BAP method gave fewer artefact peaks from reagent decomposition. The limits of detection of OA and DTX-2 were 0.4 ng on-column using BAP, which permits this method to be used for the regulatory control of these toxins in shellfish.
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- 1996
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13. Dinophysistoxin-2: the predominant diarrhoetic shellfish toxin in Ireland.
- Author
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Carmody EP, James KJ, and Kelly SS
- Subjects
- Animals, Bivalvia, Chromatography, High Pressure Liquid, Enzyme Inhibitors chemistry, Enzyme Inhibitors isolation & purification, Enzyme Inhibitors toxicity, Ethers, Cyclic chemistry, Ethers, Cyclic isolation & purification, Ethers, Cyclic toxicity, Ireland, Marine Toxins isolation & purification, Marine Toxins metabolism, Okadaic Acid, Pyrans isolation & purification, Pyrans metabolism, Reference Standards, Seawater, Stereoisomerism, Diarrhea chemically induced, Dinoflagellida metabolism, Marine Toxins toxicity, Pyrans toxicity, Shellfish Poisoning
- Abstract
Diarrhoetic shellfish poisoning (DSP) in Europe is due mainly to the presence of the dinoflagellate toxin, okadaic acid (OA). However, analysis of cultivated mussels (Mytilus edulis) from southwest Ireland revealed that an isomer of OA, dinophysistoxin-2, was the major toxin present during DSP episodes. Using fluorimetric HPLC, following derivatisation with 9-anthryldiazomethane, both OA and DTX-2 were found in shellfish during a prolonged toxic episode in 1991. However, examination of similar mussel cultivation locations in 1994 showed that DTX-2 was even more predominant. During this DSP period, OA levels were less than 0.7 microgram/g, whereas maximum DTX-2 levels of 6.3 micrograms/g hepatopancreas were recorded. This toxicity in shellfish occurred soon after high cell counts of Dinophysis acuta were observed. As well as large seasonal variability in toxin levels in rope cultured mussels, substantial variations were also observed, both horizontally and vertically, within the water column.
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- 1996
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14. Comparative studies of two organophosphorus compounds in the mouse.
- Author
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Mutch E, Kelly SS, Blain PG, and Williams FM
- Subjects
- Analysis of Variance, Animals, Biomarkers, Brain enzymology, Cholinesterase Inhibitors administration & dosage, Diaphragm enzymology, Dose-Response Relationship, Drug, Echothiophate Iodide administration & dosage, In Vitro Techniques, Isoflurophate administration & dosage, Isoflurophate toxicity, Male, Mice, Regression Analysis, Brain drug effects, Carboxylic Ester Hydrolases antagonists & inhibitors, Cholinesterase Inhibitors toxicity, Diaphragm drug effects, Echothiophate Iodide toxicity, Isoflurophate analogs & derivatives
- Abstract
A rodent model, the albino mouse, was used to investigate the in vitro and in vivo capacity of 2 organophosphate (OP) compounds, mipafox and ecothiopate, to inhibit enzymes considered to be involved in the mechanisms of OP toxicity. Mipafox and ecothiopate were chosen as model compounds because the former can produce a delayed neuropathy whereas the latter does not. Mipafox (110 mumol/kg, s.c.) inhibited brain acetylcholinesterase (AChE), neuropathy target esterase (NTE) and phenylvalerate hydrolases by 58, 64 and 65%, while diaphragm AChE and phenylvalerate hydrolases were inhibited by 66 and 80%, respectively. In contrast, ecothiopate (0.5 mumol/kg) had no effect on brain NTE or on brain or diaphragm phenylvalerate hydrolases. At the same time, diaphragm AChE was inhibited by 60% while brain AChE activity had increased by 15% of control. Mipafox was a potent inhibitor of AChE and NTE in vitro. Although ecothiopate was a highly potent anti-ChE in vitro, it had no inhibitory effect on NTE.
- Published
- 1995
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15. The origin of the effects of an anticholinesterase on the latencies of action potentials in mouse skeletal muscles.
- Author
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Kelly SS and Ferry CB
- Subjects
- Action Potentials drug effects, Action Potentials physiology, Animals, Electric Stimulation, Male, Mice, Motor Endplate drug effects, Motor Endplate physiology, Muscles innervation, Neuromuscular Junction drug effects, Neuromuscular Junction physiology, Neurotransmitter Agents metabolism, Echothiophate Iodide pharmacology, Muscles drug effects, Muscles physiology
- Abstract
1. Subcutaneous injection in mice of a single dose of an organophosphorous anticholinesterase, ecothiopate (0.5 mumol kg-1), produced increased variability in the latency (jitter) of indirectly-elicited action potentials in diaphragm muscles 5 days after treatment, but there was no effect on the variability of latencies of endplate potentials. This study was designed to elucidate the mechanism(s) of the increase in action potential jitter. 2. Action potentials evoked directly by electrical stimulation at one end of muscle fibres and recording near the other end had less jitter than indirectly-evoked action potentials and ecothiopate had no effect on directly-evoked action potentials. 3. In preparations with uncut fibres, pretreatment with ecothiopate reduced by about 20% both muscle fibre input resistance and the amplitude of spontaneous miniature endplate potentials. Ecothiopate had no effect on muscle fibre resting membrane potential or on the threshold potential for excitation. 4. In untreated preparations, indirectly-evoked action potentials recorded at the endplate had similar jitter to action potentials recorded at the tendon when latencies were measured at 10% of peak amplitude. However, when latencies were measured at peak, there was greater jitter of action potentials at the endplate. Ecothiopate increased jitter of action potentials recorded at the endplate at 10% of peak but did not significantly increase jitter of action potentials recorded at the endplate when measured at the peak. 5. In cut-fibre preparations, the first endplate potential of trains was significantly increased after ecothiopate but there was no effect of ecothiopate on the amplitude of plateau endplate potentials later in the train. Analysis of plateau endplate potentials showed that 5 days after administration, ecothiopateproduced an increase in the variance of endplate potential amplitudes and changes in the binomial parameters n and p.6. It was concluded that the increased jitter produced by ecothiopate is not a generalized effect on the plasma membrane and that none of the above observations could explain the increased jitter. The possibility is discussed that increased jitter is produced by variability in times to threshold of endplate potentials and/or by variability in the locus of generation of the action potential in the perijunctional area.
- Published
- 1994
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16. Electrophysiological and biochemical effects following single doses of organophosphates in the mouse.
- Author
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Kelly SS, Mutch E, Williams FM, and Blain PG
- Subjects
- Acetylcholinesterase metabolism, Action Potentials drug effects, Animals, Brain enzymology, Carboxylic Ester Hydrolases metabolism, Evoked Potentials drug effects, In Vitro Techniques, Isoflurophate toxicity, Male, Mice, Neuromuscular Junction physiology, Brain drug effects, Echothiophate Iodide toxicity, Isoflurophate analogs & derivatives, Neuromuscular Junction drug effects
- Abstract
Single doses of organophosphates (mipafox or ecothiopate) were given subcutaneously to mice. At intervals up to 77 days after dosing animals were killed and muscle action potentials and endplate potentials were recorded intracellularly in mouse phrenic-nerve/hemidiaphragm preparations. Activities of acetylcholinesterase and neuropathy target esterase in brain and acetylcholinesterase in diaphragm were also measured. Mipafox (0.11 mmol/kg), a neurotoxic organophosphate, produced an increase in prejunctional jitter (i.e. the variabilities of the latencies) of endplate potentials. This increase began 14-21 days after administration and lasted more than 23 days. No clinical signs of neuropathy were observed during this study. Mipafox also produced an increase in postjunctional (muscle action potential) jitter. Mipafox inhibited brain and diaphragm acetylcholinesterase and brain neuropathy target esterase. By comparison, a non-neurotoxic organophosphate, ecothiopate (0.5 mumol/kg), was a potent inhibitor of diaphragm acetylcholinesterase and produced a large increase in postjunctional jitter but ecothiopate did not inhibit brain neuropathy target esterase and had no effect on prejunctional jitter. Doses were chosen so that the inhibition of diaphragm acetylcholinesterase by each of the two organophosphates was similar. It is concluded that the neurotoxic organophosphate, mipafox, produced measurable changes in nerve function. These long-term changes may represent a new phenomenon, unrelated to the classical organophosphate induced delayed neuropathy. Alternatively, they may represent a neuropathic process which precedes or is below the threshold for clinical signs.
- Published
- 1994
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17. Protection against the effects of anticholinesterases on the latencies of action potentials in mouse skeletal muscles.
- Author
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Kelly SS, Ferry CB, Bamforth JP, and Das SK
- Subjects
- Acetylcholinesterase metabolism, Acetylcysteine pharmacology, Action Potentials drug effects, Animals, Antioxidants pharmacology, Cholinesterase Reactivators pharmacology, Electrophysiology, Male, Mice, Microelectrodes, Muscles enzymology, Pralidoxime Compounds pharmacology, Pyridostigmine Bromide pharmacology, Vitamin E pharmacology, Cholinesterase Inhibitors pharmacology, Muscles drug effects, Organophosphorus Compounds pharmacology
- Abstract
1. Adult male albino mice were injected subcutaneously with an organophosphorous anticholinesterase to initiate excessive variability in the latency of indirectly elicited muscle action potentials (jitter) when assessed 5 days later. 2. Pretreatment of the mice with a single dose of pyridostigmine prevented the development of jitter after subsequent dosing with an organophosphate. 3. Treatment with one dose of pralidoxime (2PAM) prevented the development of jitter if given less than 1 h after treatment with ecothiopate, a reactivatable inhibitor of cholinesterase. Similar treatment with 2PAM after a non-reactivatable inhibitor did not prevent the development of jitter. The repeated administration of 2PAM over 12 h did ameliorate jitter. 4. Pretreatment of mice orally with alpha-tocopherol and N-acetylcysteine, known to prevent ecothiopate-induced myopathy, did not prevent the development of jitter after ecothiopate. 5. It is concluded that the development of jitter was a consequence of the inhibition of acetylcholinesterase, and although jitter did not develop acutely, the potential for the full development of jitter was achieved about 1 h after intoxication with ecothiopate. The development of jitter did not involve the generation of free radicals. Reduction of the early effects of intoxication with anticholinesterases by pyridostigmine or 2PAM prevented the development of jitter.
- Published
- 1992
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18. Effects of suramin on the concentration--response relationship of alpha, beta-methylene ATP on the mouse vas deferens.
- Author
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Blakeley AG, Brockbank JE, Kelly SS, and Petersen SA
- Subjects
- Adenosine Triphosphate metabolism, Adenosine Triphosphate pharmacology, Animals, Female, In Vitro Techniques, Male, Mice, Mice, Inbred Strains, Muscle Contraction drug effects, Muscle, Smooth metabolism, Triazines, Vas Deferens drug effects, Vas Deferens metabolism, Adenosine Triphosphate analogs & derivatives, Muscle, Smooth drug effects, Suramin pharmacology
- Abstract
1. The effect of suramin on the concentration-effect curve for the contractile response of the isolated mouse vas deferens to alpha, beta-methylene ATP (alpha, beta-meATP) was investigated. 2. The concentration-response curve to alpha, beta-meATP had a consistent discontinuity at about 3 x 10(-6) M, giving it a biphasic appearance. 3. Suramin in a dose-dependent, reversible manner both shifted the curve to the right and at the same time elevated the maximum response. 4. The P2y inhibitor Reactive Blue 2, on the other hand, both shifted the curve to the left and elevated the maximum response. 5. These results show that alpha, beta-meATP in this preparation is an agonist both at excitatory, presumably P2y receptors and inhibitory P2y receptors, and that suramin antagonizes both effects.
- Published
- 1991
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19. The effects of anticholinesterases on the latencies of action potentials in mouse skeletal muscles.
- Author
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Kelly SS, Ferry CB, and Bamforth JP
- Subjects
- Acetylcholinesterase metabolism, Action Potentials drug effects, Animals, Atropine pharmacology, Echothiophate Iodide pharmacology, Electrophysiology, In Vitro Techniques, Isoflurophate pharmacology, Male, Mice, Motor Endplate drug effects, Organothiophosphorus Compounds pharmacology, Respiratory Muscles drug effects, Respiratory Muscles metabolism, Cholinesterase Inhibitors pharmacology, Muscles drug effects
- Abstract
1. The purpose of this investigation was to determine the long-term effects of a single dose of persistent anticholinesterases on muscle action potentials evoked by nerve stimulation. 2. Action potentials (APs), elicited by stimulation of the phrenic nerve, were recorded intracellularly in muscle fibres of mouse diaphragm. The time between stimulus and AP was measured and the variability of this latency was calculated during trains of APs. At the beginning of trains of APs there was an increase in latency, and this delay was also measured. 3. Within 3 h of subcutaneous injection, a single dose (500 nmol kg-1) of the anticholinesterase, ecothiopate produced about 90% reduction in the acetylcholinesterase activity of homogenates of mouse diaphragm muscle, but five days after injection, this activity was not different from values in untreated animals. The initial delay of APs and the variability of latencies were increased four fold and two fold respectively, remained at these maxima from the 1st to the 5th day after ecothiopate, and returned to the values in untreated animals between 15 and 27 days after ecothiopate. 4. These effects of ecothiopate on AP latency were dose-dependent and were also seen in extensor digitorum longus and soleus muscles. 5. Other anticholinesterases used were BOS (pinacolyl S-(2-trimethylaminoethyl)methylphosphonothioate), a quaternary compound, and diisopropyl fluorophosphate, a tertiary compound, which had effects similar to those of ecothiopate; the greater duration of the effects of this compound may be related to the greater duration of reduction in cholinesterase activity. 6. Ecothiopate had no effect on the delay or variability of latencies of endplate potentials which were recorded in cut-fibre preparations 5 days later. 7. It is concluded that the effects of ecothiopate on the latencies of indirectly-evoked muscle APs are postjunctional, may not be related to the degree of reduction in cholinesterase activity at the time of recording, and are not directly linked to necrosis.
- Published
- 1990
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20. Quantitative study of motor endplates in muscle fibres dissociated by a simple procedure.
- Author
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Robbins N, Olek A, Kelly SS, Takach P, and Christopher M
- Subjects
- Acetylcholinesterase metabolism, Animals, Bungarotoxins metabolism, Diaphragm ultrastructure, Female, Male, Mice, Motor Endplate metabolism, Rats, Motor Endplate ultrastructure, Neuromuscular Junction ultrastructure, Receptors, Cholinergic metabolism
- Abstract
Large numbers of single muscle fibres can be obtained reproducibly from glutaraldehyde-fixed skeletal muscle by the method described here. With suitable modifications, one can estimate acetylcholine receptor number (alpha-bungarotoxin binding sites) and endplate area in parallel portions produced from the same muscle sample, so that small differences (e.g. with growth or between muscle types) become detectable. Microdissection further increases the precision of evaluation of junctional, perijunctional and extrajunctional binding sites. Other applications are illustrated.
- Published
- 1980
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21. Bimodal miniature and evoked end-plate potentials in adult mouse neuromuscular junctions.
- Author
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Kelly SS and Robbins N
- Subjects
- Aging, Animals, Calcium pharmacology, Edrophonium pharmacology, Electric Stimulation, Evoked Potentials drug effects, In Vitro Techniques, Magnesium pharmacology, Male, Mice, Mice, Inbred Strains, Motor Endplate drug effects, Potassium pharmacology, Time Factors, Motor Endplate physiology, Neuromuscular Junction physiology
- Abstract
Intracellular recordings of spontaneous miniature end-plate potentials (m.e.p.p.s) in muscles from adult CBF-1 mice revealed a population of muscle fibres in which the amplitude distribution of m.e.p.p.s was bimodal. The large mode m.e.p.p.s were similar to those from fibres having unimodal amplitude distributions and the small mode m.e.p.p.s were about one-half to one-quarter the amplitude of the large mode. In five diverse muscle groups (extensor digitorum communis, gluteus maximus, diaphragm, extensor digitorum longus, and soleus) from mice 10-12 or 31 months of age, bimodal m.e.p.p. amplitude distributions were present in about 20% of fibres sampled. In the common bimodal distribution (type 1), the rise times of small mode m.e.p.p.s were similar to those of large mode m.e.p.p.s. A rare class of small mode m.e.p.p.s (type 2) having long rise times was also observed. Amplitudes and half-decay times of type 1 small mode m.e.p.p.s increased in the presence of an anticholinesterase (edrophonium). Increasing extracellular potassium concentration led to an increase in large mode m.e.p.p. frequency but had more variable effects on small mode frequency. In the few cases available for study, type 2 small mode m.e.p.p.s disappeared after addition of edrophonium or increased potassium. When the extracellular calcium/magnesium ratio was reduced, large mode but not small mode m.e.p.p. frequency decreased. In almost all muscle fibres in which end-plate potentials (e.p.p.s) were evoked by nerve stimulation at 20 Hz in low calcium/high magnesium solution, small mode e.p.p.s similar to small mode m.e.p.p.s appeared during 'failures' of large mode m.e.p.p.s. Also, in twelve out of fifteen fibres which had unimodal m.e.p.p. amplitude distributions, small mode e.p.p.s appeared which were similar in amplitude to small mode m.e.p.p.s in fibres with type 1 bimodal m.e.p.p.s. Thus, if both spontaneous and evoked potentials are included, small mode m.e.p.p.s are present at most CBF-1 mouse adult neuromuscular junctions independent of muscle type or animal age. Small and large mode m.e.p.p.s differ in certain responses but both are evoked by nerve stimulation at physiological frequencies and therefore participate in normal neuromuscular synaptic activity. The possible origin of small mode m.e.p.p.s is discussed.
- Published
- 1984
- Full Text
- View/download PDF
22. Comparison of the effects of pancuronium and tubocurarine on different muscles of young and old mice.
- Author
-
Kelly SS, Gertler RA, and Robbins N
- Subjects
- Animals, Diaphragm physiology, In Vitro Techniques, Male, Mice, Muscle Contraction drug effects, Neuromuscular Junction physiology, Synaptic Transmission drug effects, Aging, Muscles drug effects, Pancuronium pharmacology, Tubocurarine pharmacology
- Abstract
In order to evaluate the sensitivity of different muscle types to neuromuscular blocking drugs, a system using mouse muscles in vitro was developed and applied to detect changes in drug sensitivity in relation to age. The effect of pancuronium and tubocurarine on initial twitch and on the ratio of fourth twitch to first twitch (T4/T1) of a train-of-four at 2 Hz were compared in fast-twitch, slow-twitch and respiratory muscles in the mouse. The muscles used were: extensor digitorum longus (EDL), soleus (SOL) and diaphragm (DIA). For both drugs the order of decreasing sensitivity was EDL greater than SOL greater than DIA. This result was the same whether first twitch or T4/T1 was used, although the latter was a more sensitive indicator. The sensitivity of neuromuscular block was less in muscles from old (30-33 month) animals than in the equivalent muscles from young (8-12 month) animals.
- Published
- 1986
- Full Text
- View/download PDF
23. The effect of age on neuromuscular transmission.
- Author
-
Kelly SS
- Subjects
- Animals, Body Weight, Diaphragm physiology, Evoked Potentials, Male, Membrane Potentials, Phrenic Nerve physiology, Rats, Aging, Neuromuscular Junction physiology, Synaptic Transmission
- Abstract
1. Resting membrane potentials (RMPs), spontaneous miniature end-plate potentials (m.e.p.p.s), and evoked end-plate potentials (e.p.p.s) were recorded in phrenic nerve-hemidiaphragm preparations from rats at ages from 11 to 375 days. 2. The mean RMP increased from -64.1 +/- 1.2 mV (mean +/- S.E.) at age 11 days to -71.3 +/- 1.0 mV at age 30 days, after which there was no significant change with age. 3. The mean amplitude of m.e.p.p.s decreased from 1.088 +/- 0.070 mV at 11 days of age to 0.405 +/- 0.030 mV at 175 days of age, after which there was no significant change. 4. There was a rpaid, large increase in the frequency of m.e.p.p.s from 0.02/sec to 0.97/sec (geometric means) between 11 and 23 days of age, followed by a slower increase to 3.19/sec at 175 days of age. Subsequently there was a decrease by 2.58/sec at 375 days of age. 5. The mean of quantum content of plateau e.p.p.s elicited at a frequency of 10 Hz increased from 20.5 quanta/e.p.p. to 169.9 quanta/e.p.p. (geometric means) between 11 and 175 days of age and then decreased to 120.4 quanta/e.p.p. at 375 days of age. 6. The mean quantum content of the first e.p.p.s of trains of e.p.p.s increased from 44.2 quanta/e.p.p. to 468.8 quanta/e.p.p. (geometric means) between 11 and 175 days of age and then decreased to 358.1 quanta/e.p.p. at 375 days of age. 7. The calculated safety factor of neuromuscular transmission increased with age up to 110-175 days and subsequently decreased. 8. The change in all the above parameters occurred most rapidly in the first 6 weeks of life. The rapidity of these changes indicates that great care must be taken to ensure that control and experimental animals are adequately matched according to age, especially when rats weighing less than about 300 g are used.
- Published
- 1978
- Full Text
- View/download PDF
24. The origin of (+)-tubocurarine resistance in dystrophic mice.
- Author
-
Kelly SS, Morgan GP, and Smith JW
- Subjects
- Animals, Drug Resistance, Evoked Potentials drug effects, In Vitro Techniques, Magnesium pharmacology, Male, Mice, Muscle Contraction drug effects, Neuromuscular Junction drug effects, Receptors, Cholinergic metabolism, alpha7 Nicotinic Acetylcholine Receptor, Muscular Dystrophy, Animal physiopathology, Receptors, Nicotinic, Tubocurarine pharmacology
- Abstract
Intracellular recording, twitch responses and radio-ligand binding techniques were used to study the causes of resistance to (+)-tubocurarine (curare) of extensor digitorum longus (EDL) muscles from dystrophic mice (129 ReJ/strain). The indirectly evoked twitch response of muscles from dystrophic mice was more resistant to block by curare than the twitch response of muscles from normal littermates. The IC50 (concentration producing 50% inhibition of stimulus-evoked contractions) values for the curare block of muscle twitch were 0.78 +/- 0.03 microM and 1.32 +/- 0.05 microM (mean +/- 95% confidence limits) for muscles from normal and dystrophic mice, respectively. There was no difference between muscles from normal and dystrophic mice in the number of alpha-bungarotoxin binding sites per endplate. The amplitudes of both spontaneous miniature endplate potentials (m.e.p.ps) in unblocked preparations and of evoked endplate potentials (e.p.ps) in 1.91 microM curare were greater in muscles from dystrophic mice than in muscles from normal mice. The ratio dystrophic/normal was greater for the e.p.p. amplitudes than for the m.e.p.p. amplitudes. The quantum content of e.p.ps in magnesium-blocked and in cut-fibre preparations was greater in muscles from dystrophic mice than in muscles from normal littermates. Calculation of the binomial parameters n and p in the cut-fibre preparations indicated that this increased quantum content was caused by an increase in the value of p. It is concluded that at least part of the increased resistance to curare of the indirectly evoked twitch response of muscles from dystrophic mice is due to an increase in the quantum content of e.p.ps in these muscles.
- Published
- 1986
- Full Text
- View/download PDF
25. Statistics of neuromuscular transmitter release in young and old mouse muscle.
- Author
-
Kelly SS and Robbins N
- Subjects
- Action Potentials, Animals, Diaphragm, Hindlimb, In Vitro Techniques, Male, Mice, Motor Endplate physiology, Statistics as Topic, Aging physiology, Muscles physiology, Neurotransmitter Agents metabolism
- Abstract
1. It was reported previously that in limb muscles of old (27-30 months) CBF-1 mice, quantal content (m) of evoked transmitter release was increased compared to that in young (9-12 months) mice. In diaphragm muscles there was no change with age. The object of the present study was to determine whether the age-related increase in transmitter release was due to increase in the binomial parameter n or the parameter p. The analysis also involved consideration of goodness-of-fit between observed and expected binomial distribution of the data. 2. Spontaneous miniature end-plate potentials (m.e.p.p.s) and evoked end-plate potentials (e.p.p.s) were recorded with intracellular techniques from soleus and diaphragm muscles bathed in low-Ca high-Mg medium. The goodness-of-fit between the observed e.p.p amplitude distribution and that expected from a binomial distribution was evaluated by chi 2 test. 3. In different muscles and at different ages, the percentage of fibres with binomial e.p.p. distributions varied from 17 to 44%, even though in all fibres there was a similar proportionality between direct quantal content and the reciprocal of the square of the coefficient of variation of e.p.p. amplitudes. In addition, apparent graphical agreement between observed and theoretical binomial e.p.p. distributions was often not substantiated by the chi 2 criterion. 4. In soleus muscles from young mice, lowering the stimulus frequency from 10 to 0.5 Hz and shortening the train length from 250 to 100 pulses increased the prevalence of binomial e.p.p. distributions, but the same result was not obtained in diaphragm or soleus muscles from old mice. If the mean amplitude of groups of 10 e.p.p.s in any train showed any drift (greater than 10%) then that train was excluded from the results. Thus, in order to make valid age comparisons, only fibres with binomial e.p.p. distributions were analysed further. 5. There was no change with age in m, n or p in diaphragm muscles, but in soleus muscles from old animals a nearly 2-fold increase in n entirely accounted for the increase in m. 6. If, as proposed by others, n represents the number of release sites, then the ageing soleus neuromuscular junction may have increased numbers or length of active zones or associated membrane components.
- Published
- 1987
- Full Text
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26. The nature of the presynaptic effects of (+)-tubocurarine at the mouse neuromuscular junction.
- Author
-
Ferry CB and Kelly SS
- Subjects
- Acetylcholine metabolism, Action Potentials drug effects, Animals, Bungarotoxins pharmacology, Cholinesterase Inhibitors pharmacology, Echothiophate Iodide pharmacology, In Vitro Techniques, Male, Mice, Motor Endplate drug effects, Pancuronium pharmacology, Receptors, Cholinergic drug effects, Neuromuscular Junction drug effects, Tubocurarine pharmacology
- Abstract
1. The effects of (+)-tubocurarine (TC) on tetanic run-down and quantum content of end-plate potentials (EPPs) were investigated in cut-fibre preparations of mouse diaphragm. 2. (+)-Tubocurarine, 0.15 microM, halved the amplitude of spontaneous miniature EPPs (MEPPs) and steepened the tetanic run-down of EPPs evoked at 10 Hz by increasing the quantum content of the first EPP of the train while having no effect on quantum content of plateau EPPs. With stimulation at 1 Hz, there was little run-down and the quantum content of all EPPs was increased by TC. 3. The use of binomial statistics to analyse release indicated that after TC the increase in the quantum content of the first EPP in the train at 10 Hz was due to an increase in n and that during the run-down there was a decrease in p so that plateau EPP quantum content at 10 Hz was not different from control. 4. To elucidate a possible role of cholinoreceptors in the presynaptic effects of TC, studies were made on the effects of pancuronium or of alpha-bungarotoxin (BTX), with concentrations and exposure times where they had postsynaptic effects equal to 0.15 microM-TC. The run-down of EPPs was unaffected by BTX, while pancuronium steepened it to a lesser extent than TC. 5. The anticholinesterase, ecothiopate, decreased the quantum content of plateau EPPs only at high frequencies of stimulation (50 Hz) and did not affect the presynaptic effects of TC at 10 Hz. 6. At concentrations which reduced MEPP amplitude, atropine (10 microM) or hexamethonium (50 microM) had no effect on EPP run-down. 7. These results indicate that TC could have presynaptic effects via a presynaptic acetylcholine receptor, but that such a receptor may not have the same binding specificities as the postsynaptic receptor.
- Published
- 1988
- Full Text
- View/download PDF
27. The effect of age on the safety factor in neuromuscular transmission in the isolated diaphragm of the rat.
- Author
-
Kelly SS and Roberts DV
- Subjects
- Animals, Diaphragm physiology, In Vitro Techniques, Membrane Potentials, Motor Endplate physiology, Rats, Aging, Neuromuscular Junction physiology, Synaptic Transmission
- Abstract
An analysis of neuromuscular transmission has been made in phrenic nerve/diaphragm preparations from male rats aged 30 days or 110 days. The amplitude of miniature end-plate potentials was found to decrease with age, being 0.969 +/- SEM 0.058 mV at 30 days and 0.510 +/- SEM 0.031 mV at 110 days. Over the same period, the quantum content of the first end-plate potential of a train of 40 at 10 Hz, increased from 144.5, SEM + 11.1, -10.4 to 346, SEM +41.4, -37.0. A corresponding change was observed also in the average quantum contents of the last 30 end-plate potentials of each train; from 50.6, SEM +3.5, -3.2, to 138.9, SEM + 15.0,--13.6. The safety factor for neuromuscular transmission, calculated from these measured parameters, was found at 30 days to be only 70-80% of that at 110 days. It was estimated that the lower safety factor found in young rats was approximately equivalent to the neuromuscular blocking action of a dose of, at least, 0.0225 mg/kg of d-tubocurarine. Extrapolation of these results to man would support previous reports of increased sensitivity to d-tubocurarine in neonates.
- Published
- 1977
- Full Text
- View/download PDF
28. Modified technique for maxillary denture suspension.
- Author
-
Sanders B, Kelly SS, and Adams DR
- Subjects
- Humans, Denture Retention methods, Denture, Complete, Upper
- Published
- 1978
29. Neuromuscular transmission and correlative morphology in young and old mice.
- Author
-
Banker BQ, Kelly SS, and Robbins N
- Subjects
- Acetylcholine, Aging, Animals, Bungarotoxins pharmacology, In Vitro Techniques, Membrane Potentials, Mice, Mice, Inbred Strains, Microscopy, Electron, Neuromuscular Junction ultrastructure, Receptors, Cholinergic drug effects, Neuromuscular Junction physiology, Synaptic Transmission
- Abstract
1. Age changes in spontaneous and evoked transmitter release, in receptor number and in ultrastructure at the neuromuscular junction were studied in the CBF-1 mouse strain, which stays physically active and relatively free of organ pathology into advanced age.2. Spontaneous miniature end-plate potentials (m.e.p.p.s) were recorded in the following young (8-12 months) and old (29-33 months) mouse muscles: extensor digitorum longus (e.d.l.), soleus (sol.), gluteus maximus (g.m.), diaphragm (diaph.) and extensor digitorum communis (e.d.c.).3. M.e.p.p. amplitudes were unchanged with age in four muscle groups despite increases in input resistance (in e.d.l., sol. and g.m.). M.e.p.p. amplitude in old diaph. increased 54% with no change in input resistance. Bimodal distributions of m.e.p.p. amplitudes were observed in 6-23% of muscle fibres but were not more prevalent in old mice. There was little or no change in resting membrane potential with age.4. Numbers of junctional acetylcholine receptors (measured with (125)I-alpha-bungarotoxin) were the same in all young and old muscles except e.d.l., where a 30% decrease was noted. Extrajunctional receptors and other indicators of denervation (decreases in resting potential, twitch tension or muscle fibre diameter) were absent or minimal.5. M.e.p.p. frequency decreased in e.d.l., sol. and e.d.c. but not in g.m. or diaph. There was no correlated change in the cholinesterase-positive end-plate area.6. It is concluded that m.e.p.p. amplitude is maintained in old muscles by a combination of compensatory changes. The decline in m.e.p.p. frequency varies between muscle groups and is independent of the length of the motoneurone axon or level of innervation.7. Evoked end-plate potentials (e.p.p.s) were recorded in e.d.l., sol. and diaph. from young (11-13 months) and old (29-30 or 34-35 months) male CBF-1 mice in curarized preparations stimulated at 2 or 20 Hz. The amplitude of the initial e.p.p. of the trains was increased by 122% in old e.d.l. and 93% in old sol., and plateau e.p.p. amplitudes were also increased by about 100% (e.d.l.) and 67% (sol.). This, combined with the absence of change in m.e.p.p. amplitude with age, suggests that the number of quanta released per nerve impulse was increased. In diaph. there was no change with age.8. In all muscle groups, the threshold for initiation of the muscle action potential was unchanged with age. Thus, the relative safety factor of transmission was increased in curarized old e.d.l. and sol. (but not diaph.).9. Depression of the indirect twitch in solutions with a decreased calcium: magnesium ratio was also used as a relative measure of synaptic efficacy. Old sol. and e.d.l. but not diaph. muscles showed less depression of indirect twitch amplitude than did young muscle under these conditions.10. In cut-fibre preparations of sol. and diaph. stimulated at 20 Hz, there was no age-dependent difference in e.p.p. amplitude, in directly measured quantal content, or in curare sensitivity. In view of other results, these findings require careful interpretation.11. Ultrastructural morphometry was carried out in e.d.l. The nerve terminals in old (30 and 34 months) e.d.l. muscles exhibited pronounced loss of synaptic vesicles. In 34-month animals, decreased nerve terminal area and post-synaptic folds devoid of nerve terminals were often observed. Since no evidence of denervation was found by physiological criteria, it is concluded that in 34-month mice, nerve terminals withdraw from some synaptic gutters but do not abandon any junction entirely. The large presynaptic ultrastructural changes contrast with the physiological data showing no deficit and even increases in transmitter release. Therefore, under these conditions, these profound structural changes are either not functionally significant or are well compensated.
- Published
- 1983
- Full Text
- View/download PDF
30. The effect of nutritional state on neuromuscular transmission in the rat.
- Author
-
Kelly SS
- Subjects
- Age Factors, Animal Nutritional Physiological Phenomena, Animals, Body Weight, Diaphragm physiology, Male, Membrane Potentials, Quantum Theory, Rats, Diet, Neuromuscular Junction physiology, Synaptic Transmission
- Abstract
1. Evoked end-plate potentials (e.p.p.s) were recorded in phrenic nerve-hemidiaphragm preparations from rats which had been subjected to periods of dietary restriction. 2. The mean quantum content of the first e.p.p. of trains of e.p.p.s was significantly increased after 1 week of dietary restriction in 30-day-old but not in 110-day-old rats. 3. The mean quantum content of plateau e.p.p.s elicited at a frequency of 10 Hz was not significantly affected by brief periods of dietary restriction in either 30-day-old or 110-day-old rats. 4. In the younger animals there was found to be a decrease in the safety factor of neuromuscular transmission following dietary restriction when this parameter was calculated using previously reported values for the amplitude of spontaneous miniature end-plate potentials (m.e.p.p.s) after such a restricted diet. 5. Such rapid changes in neuromuscular transmission following brief periods of dietary restriction indicate that great care is required in the choice of adequate control animals when food intake is altered by experimental procedures.
- Published
- 1979
- Full Text
- View/download PDF
31. Progression of age changes in synaptic transmission at mouse neuromuscular junctions.
- Author
-
Kelly SS and Robbins N
- Subjects
- Animals, Magnesium pharmacology, Male, Membrane Potentials drug effects, Mice, Motor Endplate drug effects, Motor Endplate physiology, Muscles innervation, Neuromuscular Junction drug effects, Tubocurarine pharmacology, Aging, Neuromuscular Junction physiology, Synapses physiology, Synaptic Transmission drug effects
- Abstract
The progression of age-related changes in neuromuscular function was investigated in muscles from CBF-1 mice between 7 and 32 months of age. End-plate potentials (e.p.p.s) were recorded in extensor digitorum longus (e.d.l.), soleus, and diaphragm muscles after neuromuscular transmission was blocked with either (+)-tubocurarine chloride (curare) or high-Mg/low-Ca Krebs solutions. Between 10 and 31 months of age in e.d.l. and soleus but not in diaphragm, there was an increase in e.p.p. amplitude with age. In soleus this increase was approximately two-fold in curare and three-fold in high-Mg solution. Increase in e.p.p. amplitude in curarized preparations took place between 20 and 28 months of age in e.d.l. and between 28 and 31 months of age in soleus. Indirectly elicited twitch responses were used to determine the time course of age-related changes in sensitivity to Mg block. Increased resistance to block appeared between 15 and 19 months of age in both e.d.l. and soleus (in which the increase was more gradual). E.d.l. muscles from 25-month-old CFW mice also showed an increased resistance to Mg block compared to those from 7-8-month-old animals. In Mg-blocked preparations, increased quantum content (measured directly) accounted for the increased e.p.p. amplitude. Spontaneous miniature end-plate potential (m.e.p.p.) frequency in old soleus muscles was not sensitive to low-Ca/high-Mg solutions although frequency in young soleus and young and old diaphragm was significantly reduced. It is concluded that age-related changes in evoked transmitter release begin in mid life and take place more rapidly in e.d.l. than in soleus.(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1983
- Full Text
- View/download PDF
32. Dietary restriction and miniature end-plate potentials [proceedings].
- Author
-
Kelly SS
- Subjects
- Animals, Body Weight, Diaphragm physiology, Diet, Rats, Membrane Potentials, Nutrition Disorders physiopathology
- Published
- 1978
33. Sustained transmitter output by increased transmitter turnover in limb muscles of old mice.
- Author
-
Kelly SS and Robbins N
- Subjects
- Animals, Curare pharmacology, Electric Stimulation, Extremities, Male, Mice, Motor Endplate physiology, Muscle Contraction, Time Factors, Aging, Muscles metabolism, Neurotransmitter Agents metabolism
- Abstract
The ability of neuromuscular junctions in old animals to maintain tetanic output was tested in phasic and tonic limb muscles and the physiologic mechanism of maintenance was elucidated by analysis of the turnover of a false transmitter during prolonged tetani. Transmitter release during and after tetani was compared in limb muscles of young (8-9 month) and old (28-30 month) male CBF-1 mice. Amplitudes of end-plate potentials (epp's) in curarized preparations and of spontaneous miniature end-plate potentials (mepp's) were measured in vitro at 30 degrees C in soleus and extensor digitorum longus (edl) muscles. In both young and old soleus muscles, epp amplitude was maintained at about 45% of resting level during the latter part of trains of 1,200 stimuli at 10 Hz but recovered to about 90% control within a few seconds after stimulation ceased. In edl muscles of young mice, epp amplitudes during a 20 Hz train of 1,200 impulses steadily declined to about 20% of control and gradually recovered over 2 min after the tetanus. In old edl muscles, tetanic decay of the epp's was greater and recovery slower than in young muscles, but absolute epp amplitudes were invariably greater. During trains of 6,000 impulses at 10 Hz, plateau epp amplitude decayed to 40-50% in young soleus muscle and 30-40% control in old muscle, but recovery was similar and absolute epp amplitudes were greater in old soleus muscle. A false transmitter precursor, homocholine (HoCh), was used to investigate the mechanism of this prolonged output, and, therefore, the use of HoCh in this system was first validated.(ABSTRACT TRUNCATED AT 250 WORDS)
- Published
- 1986
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