Search PubMed⌕ Search

Biomedical subjects

M A Lynch

Publications and source records attributed to M A Lynch.

At least 109 records · Page 6Linked to original sources
PubMed1987

Increase in K+-stimulated, Ca2+-dependent release of [3H]glutamate from rat dentate gyrus three days after induction of long-term potentiation.

Long-term potentiation (LTP) was induced by unilateral tetanic stimulation of the perforant path in the dentate gyrus of rats with implanted electrodes. Evoked potentials were monitored for the subsequent 3 days in one group, and for 23 days in another. The dentate gyrus was removed bilaterally and slices prepared and stored in 10% DMSO/Krebs for subsequent analysis of K+-stimulated, Ca2+-dependent release of [3H]glutamate. In the 3-day group, in which the mean increase in the population EPSP was 35% at the time of sacrifice, release from the tetanized side was significantly greater than from the unstimulated side. In the 23-day group, both the increase in the EPSP and the increase in release from the tetanized side had declined to statistically insignificant levels. These results extend to a period of several days the previously observed association between LTP and increased K+-stimulated, Ca2+-dependent release of transmitter.

Animals↗
PubMed1987

Increase in [3H]glutamate release from slices of dentate gyrus and hippocampus following classical conditioning in the rat.

The release of amino acids was examined in three hippocampal areas following classical conditioning. Paired or unpaired tone(CS)-shock(US) presentations were given to animals engaged in a previously acquired food-motivated lever-pressing task. Conditioned suppression of lever-pressing was the behavioural measure of conditioning. The dentate gyrus and areas CA1 and CA3 of the hippocampus were removed bilaterally from conditioned and pseudoconditioned animals, and slices cut and stored in liquid nitrogen for subsequent in vitro analysis of the release of radiolabelled glutamate and aspartate. K+-stimulated release of radiolabelled amino acids was analysed in the presence and absence of extracellular Ca2+. Potassium-stimulated, Ca2+-dependent release of [3H]glutamate was significantly greater in slices of dentate gyrus and area CA1 prepared from conditioned animals than from pseudoconditioned animals. This finding identifies a neurochemical change associated with classical conditioning which is similar to the increase in transmitter release seen in hippocampal long-term potentiation (LTP), and which is consistent with the hypothesis that an LTP-like mechanism is involved in mnemonic processes.

Animals↗
PubMed1987

Long-term potentiation in the dentate gyrus: induction and increased glutamate release are blocked by D(-)aminophosphonovalerate.

D(-)Aminophosphonovalerate, a specific antagonist of the N-methyl-D-aspartate subtype of glutamate receptor, was perfused through a push-pull cannula into the dentate gyrus of rats anaesthetized with urethan in order to observe its effect on the induction and maintenance of long-term potentiation and on the increase in release of endogenous glutamate associated with long-term potentiation. The amplitude of the population spike evoked by single test shocks to the perforant path was significantly depressed by 100 microM D(-)aminophosphonovalerate, but there was a minimal effect on the slope of the population excitatory postsynaptic potential, or on the concentration of glutamate released into the perfusate. A brief high-intensity tetanus given to the perforant path while D(-)aminophosphono-valerate was being perfused failed to induce long-term potentiation or the sustained increase in glutamate release associated with long-term potentiation. Short-term post-tetanic potentiation was not affected. After wash-out of D(-)aminophosphonovalerate, a second high-frequency train produced both long-term potentiation and an increase in glutamate release which was sustained for the subsequent 1 h period of observation. D(-)Aminophosphonovalerate did not suppress long-term potentiation once it had been induced. D(-)Aminophosphonovalerate (100 microM) did not itself affect in vivo release of glutamate. However, in a separate series of in vitro experiments, D(-)aminophosphonovalerate at concentrations of 50 microM and above was found to depress the Ca2+ -dependent, K+-stimulated release of preloaded [14C]-glutamate from dentate slices.(ABSTRACT TRUNCATED AT 250 WORDS)

2-Amino-5-phosphonovalerate↗
PubMed1987

Vascularity for healing of meniscus repairs.

Vascularity in the human meniscus is poor beyond 1-2 mm from the meniscosynovial junction, yet 22% of the tears in this series occur with a greater than or equal to 3-mm peripheral white rim. It is possible to suture these tears with the wider peripheral white rims, but healing rates are reduced because it is more difficult to obtain a satisfactory vascular supply. This article describes the history of our efforts at obtaining blood supply for healing of meniscus tears with a peripheral white rim up to 5 mm. Resection of the peripheral white rim to the vascular bed was unsatisfactory because it reduced the size of the meniscus and, by 3 years, the subsequent degenerative changes in the knee were comparable to meniscectomy. Holes made in the rim with a biopsy needle were again unsuccessful at improving healing. The present technique involves using rasps to abrade the parameniscal synovium on both the superior and inferior surface of the peripheral white rim. None of the peripheral white rim is resected. In the first series of 240 patients in whom peripheral white rim resection or the biopsy punch was used, the failure rate of meniscus healing was 22%. In a subsequent series of 68 patients (52 males, 16 females) who had 81 meniscal repairs by means of the rasp for parameniscal synovial abrasion, the failure rate was 9%. The rasp appears to be the safest and most effective method to gain vascularity for healing of meniscus repairs. It is possible to obtain healing with 5-mm peripheral white rims without resection of any portion of this rim, thus maintaining the full size of the meniscus.

Adolescent↗
PubMed1987

Sulfate transport by chick renal tubule brush-border and basolateral membranes.

Brush-border and basolateral membrane vesicles (BBMV and BLMV, respectively) were prepared from chick kidney by a calcium precipitation method and by centrifugation on an 8% Percoll self-generating gradient, respectively. In BBMV a 100-mM Na gluconate gradient, out greater than in, caused concentrative sulfate uptake approximately fivefold greater at 1 min than at 60 min (equilibrium) whether or not the membranes were short-circuited with 100 mM K gluconate, in = out, plus 20 micrograms valinomycin/mg protein. A 48-mM HCO3- gradient, in greater than out, stimulated a 2.5-fold higher uptake at 1 min than at 60 min, and short circuiting as above had no effect on the magnitude of this response. Imposition of a H+ gradient (pH 5.4 out vs. pH 7.4 in) caused concentrative uptake fourfold higher at 1 min than at equilibrium. Short circuiting as above or addition of 0.1 mM carbonyl cyanide m-chlorophenylhydrazone (CCCP) significantly inhibited the pH gradient effect. Creation of an inside positive electrical potential with 100 mM K gluconate, out greater than in, plus valinomycin, also caused concentrative sulfate uptake. The K gradient in the absence of valinomycin had no effect on sulfate uptake (compared with isosmotic mannitol). Based on inhibitor/competitor effects, these are distinct sulfate transport processes. In chick BLMV, imposition of an HCO3- gradient, in greater than out, produced concentrative sulfate uptake; however, neither Na+ nor H+ gradients had significant effects at 15 s. 4-Acetamido-4'-isothiocyanostilbene 2,2'-disulfonic acid disodium at 0.1 mM was an effective inhibitor of BLMV bicarbonate-sulfate exchange; however, neither Cl-, SCN-, nor CCCP inhibited.

Animals↗
PubMed1986

Long-term potentiation of synaptic transmission in the hippocampus of the rat; effect of calmodulin and oleoyl-acetyl-glycerol on release of [3H]glutamate.

The effect of calmodulin (CaM) and oleyl-acetyl-glycerol (OAG, a synthetic analogue of diacylglycerol, DAG) on K+-induced release of radiolabelled glutamate (Glu), was examined in synaptosomes prepared from area CA3 of control rats and rats in which long-term potentiation (LTP) had been induced in vivo by a brief train of high-frequency stimulation. Both CaM and OAG significantly enhanced release from control tissue in a dose-dependent manner. Release of preloaded L-[3H]Glu was significantly greater in synaptosomes prepared from potentiated tissue than from control tissue but neither CaM nor OAG further enhanced release in potentiated preparations. The occlusion of the two effects suggests that CaM and endogenous DAG are likely to be involved in control of Glu release and the enhancement of release associated with LTP.

Animals↗
PubMed1986

On the mechanism of enhanced release of [14C]glutamate in hippocampal long-term potentiation.

K+-induced release of [14C]glutamate was studied in slices of dentate gyrus prepared from control rats and rats in which long-term potentiation (LTP) had been induced in vivo. At all concentrations of Ca2+ studied, release from potentiated slices was greater than from control slices. In the same preparations both Ruthenium Red and caffeine enhanced basal release but in potentiated tissue the Ruthenium Red-induced release was significantly greater than in control tissue. These results are discussed in the light of our recent finding that enhanced transmitter release is associated with LTP.

Animals↗
PubMed1986

Long-term potentiation is associated with an increase in calcium-dependent, potassium-stimulated release of [14C]glutamate from hippocampal slices: an ex vivo study in the rat.

Long-term potentiation (LTP) was induced in the commissural pathway to CA3 in vivo. Tissue slices were prepared from potentiated and control hippocampi and preloaded with [14C]glutamate ([14C]glu). K+-stimulated release of [14C]glu from these slices was compared in the absence and presence of extracellular Ca2+. High-affinity uptake and Ca2+-independent release of [14C]glu were not affected by the induction of LTP, but Ca2+-dependent release from potentiated tissue was significantly greater than that from control tissue. These results demonstrate that LTP induced in vivo in the commissural pathway to CA3 is associated with enhanced release of preloaded glutamate in vitro.

Animals↗
PubMed1986

Noradrenaline modulates the release of [14C]glutamate from dentate but not from CA1/CA3 slices of rat hippocampus.

The modulation of the release of [14C]glutamate by noradrenaline (NA) was investigated in slices prepared from the dentate gyrus and from the CA1/CA3 area of the hippocampus. In dentate, but not in CA1/CA3 slices, NA significantly enhanced K+-induced Ca2+-dependent release, and this effect was mimicked by clonidine and isoprenaline, but not by phenylephrine. The enhancement of release by NA was antagonised by propranolol, but not by yohimbine or phentolamine. These results suggest that NA does not modulate the release of glutamate in CA1/CA3, but does so in the dentate gyrus, probably by acting on presynaptically-located beta receptors.

Animals↗
PubMed1986

In-vitro release of [14C]glutamate from dentate gyrus is modulated by GABA.

The effect of GABA (10(-3) and 10(-4) M) on the release of preloaded [14C]glutamate from slices of rat dentate gyrus, in response to K+ stimulation, was studied in Ca2+-free and normal Krebs solutions. Release in Ca2+-free solution was significantly enhanced, but there was no change in release in normal Krebs solution. These results imply that Ca2+-dependent (presumably neuronal) release of glutamate from the dentate gyrus is depressed by GABA, while non-neuronal Ca2+-independent release is enhanced.

Animals↗
PubMed1986

Correlation between long-term potentiation and release of endogenous amino acids from dentate gyrus of anaesthetized rats.

The relationship between long-term potentiation (l.t.p.) and the release of endogenous amino acid transmitters has been investigated in the dentate gyrus of rats anaesthetized with urethane. The molecular layer was perfused with artificial cerebrospinal fluid using a push-pull cannula. The perfusate was collected and analysed for glutamate, aspartate, glycine, glutamine and gamma-aminobutyric acid (GABA) using high-performance liquid chromatography (h.p.l.c.) with fluorometric detection. Recording electrodes were attached to the cannula to enable responses evoked by test stimuli to the perforant path to be monitored in the molecular and cell body layers. Perfusion was continued for 3 h while test stimuli were delivered to the perforant path at 30 s intervals. In the control group (n = 8), no further stimulation was given. In a second group (n = 8), a single high-frequency train (250 Hz for 200 ms) was delivered at the end of the first hour to induce l.t.p. The average potentiation of the slope of the excitatory post-synaptic potential (e.p.s.p.) 2 h later was 15%. In a third group (n = 8), the train to the perforant path was paired with a train to the commissural input to the dentate gyrus, a procedure which blocks the induction of l.t.p. In the potentiated group, there was an increase in the concentrations of glutamate and aspartate following the induction of l.t.p., relative to the decline seen in corresponding periods of the control group. This increase remained statistically significant for 1.5 h in the case of glutamate and for 45 min in the case of aspartate. There were no l.t.p.-associated changes in the release of glutamine or glycine; there was an indication that l.t.p. may be associated with a decrease in the release of GABA. Increasing the frequency and intensity of perforant path activation resulted in enhanced concentrations of glutamate and aspartate in the perfusate; no such changes occurred when granule cells were activated antidromically. We discuss the origin of the relative increases in the concentration of glutamate and aspartate which are found in the perfusate following the induction of l.t.p. and conclude that the most likely source is a sustained increase in activity-dependent release of these amino acids from perforant path terminals.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1985

Long-term potentiation of synaptic transmission in the dentate gyrus: increased release of [14C]glutamate without increase in receptor binding.

High-affinity uptake, K+-induced release and Cl -dependent binding of radiolabelled glutamate were examined in vitro in tissue prepared from the dentate gyrus of rats in which long-term potentiation (LTP) had been induced in vivo by a brief train of high-frequency stimulation. Release of preloaded L-[14C]glutamate was significantly greater in slices prepared from potentiated tissue than from control tissue. Uptake and binding were not significantly different. Release and uptake of L-[3H]aspartate were also studied in the same tissue: no significant difference was seen between the two groups. These results provide further evidence for an association between LTP and increased glutamate release but are inconsistent with previous reports that LTP is accompanied by an increase in glutamate binding.

Animals↗
PubMed1985

Altered characteristics of [3H]dopamine release from superfused slices of corpus striatum obtained from rats receiving ethanol in vivo.

Ethanol, 50 mM, in vitro inhibited the release of [3H]dopamine ([3H]DA) induced by depolarisation with 40 mM K+ from slices of corpus striatum of the rat. In contrast, the release of [3H]DA induced by the Ca2+ ionophore (A23187) was enhanced by the presence of ethanol in vitro. When similar preparations were obtained from brains of rats which had received ethanol in vivo chronically by inhalation for 5-7 days the characteristics of release of [3H]DA were altered. Thus, the inhibitory effect of ethanol in vitro on release induced by K+-depolarisation was lost, as was the enhancing effect of ethanol on the release induced by A23187. When release of [3H]DA was studied in the absence of added ethanol the fraction of stored 3H released either by K+-depolarisation or by A23187 was increased in the preparations from animals which had received ethanol in vivo. Similar changes in release induced by A23187, though of lesser magnitude, could be seen in rats which had received ethanol acutely (3 g kg-1 i.p.; 30 min). An even greater fraction of [3H]DA was released by A23187 in preparations from rats which had been made physically dependent on ethanol. These changes in the release characteristics of [3H]DA were still apparent in animals undergoing a physical syndrome of withdrawal from ethanol. The results are discussed in relation to the cellular basis for the development of tolerance to and dependence on ethanol.

Animals↗
PubMed1985

Child abuse before Kempe: an historical literature review.

This literature review traces the recognition of child abuse and ends where many texts begin with the publication of Henry Kempe's paper in 1962, where the term, "battered child syndrome," was used for the first time. Starting with the first known treatise in pediatrics, the review examines evidence produced throughout the centuries on the recognition of physical child abuse. Many of the references are medical and show how while the early physicians found it easy to accept that those caring for children might injure them, by the end of the 19th century, more obscure diagnoses were being sought to explain the lesions. However, even during the time some physicians were pursuing "scientific" etiologies, there are publications that demonstrate a continuing acknowledgment of the problem of child abuse. No review of this type can claim to be complete, and the author hopes others will be sufficiently interested to seek out further historical references.

Child↗
PubMed1985

Low doses of T3 induce a rapid metabolic response in young lambs.

Injection of 1 microgram/kg T3 resulted in an increase in metabolic rate (VO2) within an hour of administration to lambs (aged 27 to 180 h). A larger dose of 5 micrograms/kg T3 initially caused a slight inhibition of VO2, which was followed in the second post-injection hour by a significant increase. The increase in VO2 during the second post-injection hour after either 1 microgram/kg or 5 micrograms/kg T3 represented a rise of 22% above pre-injection VO2. The increase persisted and was slightly enhanced during the third post-injection hour. These changes were significantly greater than the smaller changes which followed control injection (P less than 0.005). No significant changes in Tre or Tesk occurred after any treatment. This rapid response to low, physiological doses of T3 emphasises a possible role for thyroid hormones in the short-term control of metabolism in young animals.

Animals↗
PubMed1985

Administration of low doses of TSH result in a rapid increase in the metabolic rate of young lambs.

A low dose of TSH (Thyroid Stimulating Hormone) can induce a rapid increase in VO2 and the response is dose dependent. Lambs aged 36 to 289 h were used. 5.0 i.u./kg TSH, the highest dose used, caused an initial inhibition of response but during the second and third post injection hours VO2 increased to control level. The intermediate TSH dose, 1.0 i.u./kg TSH resulted in a clear increase in VO2 even in the first post-injection hour, which further increased in the second and third hours. This change was significantly greater than in controls. Animals treated with the lowest dose, 0.5 i.u./kg TSH divided themselves into 2 distinct populations: responders, where an immediate and significant increase in VO2 occurred and non responders, where a small inhibition of metabolism was evident. The responder group had a significantly lower pre-injection VO2 and a significantly lower mean body weight, than the non responders. In the responders, the stimulation of metabolism was greater than at either of the higher TSH doses. These results indicate that low, but not high doses of TSH induce a rapid metabolic response. The argument in favour of a short-term role for thyroid hormones is thus strengthened.

Animals↗