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R S Jones

Publications and source records attributed to R S Jones.

At least 37 records · Page 2Linked to original sources
PubMed2001

NR2B-containing NMDA autoreceptors at synapses on entorhinal cortical neurons.

We have previously shown that presynaptic N-methyl-D-aspartate receptors (NMDARs) can facilitate glutamate release onto principal neurons in the entorhinal cortex (EC). In the present study, we have investigated the subunit composition of these presynaptic NMDARs. We recorded miniature alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor-mediated excitatory postsynaptic currents (mEPSCs), from visually identified neurons in layers II and V of the EC in vitro. In both layers, bath application of the NR2A/B subunit-selective agonist, homoquinolinic acid (HQA), resulted in a marked facilitation of mEPSC frequency. Blockade of presynaptic Ca(2+) entry through either NMDARs or voltage-gated Ca(2+) channels with Co(2+) prevented the effects of HQA, confirming that Ca(2+) entry to the terminal was required for facilitation. When the NR2B-selective antagonist, ifenprodil, was applied prior to HQA, the increase in mEPSC frequency was greatly reduced. In addition, we found that an NMDAR antagonist blocked frequency-dependent facilitation of evoked release and reduced mEPSC frequency in layer V. Thus we have demonstrated that NMDA autoreceptors in layer V of the EC bear the NR2B subunit, and that NMDARs are also present at terminals onto superficial neurons.

2-Amino-5-phosphonovalerate↗
PubMed2001

Autobiographical memory and parasuicide in borderline personality disorder.

BACKGROUND: Several studies have found that parasuicidal patients are poor at recalling specific autobiographical memories when tested with the word-cueing paradigm and two studies have reported some evidence that over-general recall is a risk factor for repetition of parasuicide. The aim of the present study was to test whether this association could be replicated with a sample of patients suffering from borderline personality disorder (BPD). METHOD: Twenty-three patients with BPD completed a version of the Autobiographical Memory Test (AMT) and self-report measures of depression, anxiety and trait anger. In a structured interview, they also reported the number of times they had engaged in parasuicidal acts during the previous 4 months. RESULTS: The number of general memories produced on the AMT made a significant contribution to the prediction of the frequency of parasuicidal acts in a multiple regression analysis but the partial correlation in the final equation was negative. That is, those who showed greatest over-general recall reported fewest parasuicidal acts. Anxiety and depression, but not trait anger, also made significant independent contributions to the prediction of parasuicide. CONCLUSION: Over-general autobiographical recall may help to protect borderline individuals from parasuicidal acts by helping them to avoid distressing memories.

Adolescent↗
PubMed2001

Debunking the pathological model--the functions of an Internet discussion group.

In recent years there has been a profusion of resources about Down syndrome available on the World Wide Web and for increasing numbers of people the internet is the resource first contacted when new information is required on a topic. The present paper examined the function of a discussion group which is used primarily by parents of people with Down syndrome. Qualitative research methodology (content analysis) was used to analyse the daily discussions over a 5 month period in 1998 (February to July) and over a 2-week follow up period six months later (January 1999). The analysis revealed themes of celebration, seeing the child before seeing the handicap, hope and optimism, a sense of purpose in life and of being like a family within this group.

Communication↗
PubMed2000

The anticonvulsant, lamotrigine decreases spontaneous glutamate release but increases spontaneous GABA release in the rat entorhinal cortex in vitro.

It has been suggested that the anticonvulsant effect of lamotrigine resides with it's ability to block voltage gated Na-channels at presynaptic sites, thus stabilizing the presynapse, and, consequently, reducing the release of synaptic transmitters. Neurochemical studies have shown that it can inhibit the veratrine-stimulated release of the excitatory transmitter, glutamate from cortical tissue, but that at slightly higher concentrations it also reduces the release of the inhibitory transmitter, GABA. In the present study we examined the effect of the drug on the release of these transmitters at synapses in the rat entorhinal cortex, using the whole-cell patch clamp technique to record spontaneous excitatory (EPSCs) and inhibitory postsynaptic currents (IPSCs). Lamotrigine reduced the frequency, but not the amplitude of spontaneous EPSCs. This clearly indicated a presynaptic effect to reduce the release of glutamate. However, the same effect was observed when we tested the drug on miniature EPSCs, recorded in the presence of TTX and Cd, showing that blockade of Na-channels or Ca-channels was not a prerequisite for inhibition of glutamate release. In contrast to it's effects on EPSCs, lamotrigine increased both the frequency and amplitude of spontaneous IPSCs, suggesting that the drug was acting presynaptically to enhance GABA release. Again, similar effects were seen with miniature IPSCs recorded in TTX. These opposite effects of lamotrigine on glutamate and GABA release are similar to those we have reported previously with phenytoin, and suggest that reciprocal modulation of the background release of the major excitatory and inhibitory transmitters may be a significant factor in dampening excitability in pathologically hyperexcitable cortical networks.

Animals↗
PubMed2000

Laminar differences in recurrent excitatory transmission in the rat entorhinal cortex in vitro.

Paired intracellular recordings were used to investigate recurrent excitatory transmission in layers II, III and V of the rat entorhinal cortex in vitro. There was a relatively high probability of finding a recurrent connection between pairs of pyramidal neurons in both layer V (around 12%) and layer III (around 9%). In complete contrast, we have failed to find any recurrent synaptic connections between principal neurons in layer II, and this may be an important factor in the relative resistance of this layer in generating synchronized epileptiform activity. In general, recurrent excitatory postsynaptic potentials in layers III and V of the entorhinal cortex had similar properties to those recorded in other cortical areas, although the probabilities of connection are among the highest reported. Recurrent excitatory postsynaptic potentials recorded in layer V were smaller with faster rise times than those recorded in layer III. In both layers, the recurrent potentials were mediated by glutamate primarily acting at alpha-amino-3-hydroxy-5-methyl-4-isoxazole receptors, although there appeared to be a slow component mediated by N-methyl-D-aspartate receptors. In layer III, recurrent transmission failed on about 30% of presynaptic action potentials evoked at 0.2Hz. This failure rate increased markedly with increasing (2, 3Hz) frequency of activation. In layer V the failure rate at low frequency was less (19%), and although it increased at higher frequencies this effect was less pronounced than in layer III. Finally, in layer III, there was evidence for a relatively high probability of electrical coupling between pyramidal neurons. We have previously suggested that layers IV/V of the entorhinal cortex readily generate synchronized epileptiform discharges, whereas layer II is relatively resistant to seizure generation. The present demonstration that recurrent excitatory connections are widespread in layer V but not layer II could support this proposal. The relatively high degree of recurrent connections and electrical coupling between layer III cells may be a factor in it's susceptibility to neurodegeneration during chronic epileptic conditions.

2-Amino-5-phosphonovalerate↗
PubMed2000

Reciprocal modulation of glutamate and GABA release may underlie the anticonvulsant effect of phenytoin.

Although conventional wisdom suggests that the effectiveness of phenytoin as an anticonvulsant is due to blockade of Na+-channels this is unlikely to be it's sole mechanism of action. In the present paper we examined the effects of phenytoin on evoked and spontaneous transmission at excitatory (glutamate) and inhibitory (GABA) synapses, in the rat entorhinal cortex in vitro. Evoked excitatory postsynaptic potentials at glutamate synapses exhibited frequency-dependent enhancement, and phenytoin reduced this enhancement without altering responses evoked at low frequency. In whole-cell patch-clamp recordings the frequency of excitatory postsynaptic currents resulting from the spontaneous release of glutamate was reduced by phenytoin, with no change in amplitude, rise time or decay time. Similar effects were seen on miniature excitatory postsynaptic currents, recorded in the presence of tetrodotoxin. Evoked inhibitory postsynaptic potentials at GABA synapses displayed a frequency-dependent decrease in amplitude. Phenytoin caused a reduction in this decrement without affecting the responses evoked at low frequency. The frequency of spontaneous GABA-mediated inhibitory postsynaptic currents, recorded in whole-cell patch mode, was increased by phenytoin, and this was accompanied by the appearance of much larger amplitude events. The effect of phenytoin on the frequency of inhibitory postsynaptic currents persisted in the presence of tetrodotoxin, but the change in amplitude distribution largely disappeared. These results demonstrate for the first time that phenytoin can cause a simultaneous reduction in synaptic excitation and an increase in inhibition in cortical networks. The shift in balance in favour of inhibition could be a major factor in the anticonvulsant action of phenytoin.

2-Amino-5-phosphonovalerate↗
PubMed2000

On-line quantitative analysis of surface electromyography of the pelvic floor in patients with faecal incontinence.

BACKGROUND: Needle electromyography (EMG) remains the 'gold standard' for the assessment of external anal sphincter innervation. It is, however, an invasive and poorly tolerated technique. In this study a quantitative form of surface electromyography was compared with needle EMG of the external anal sphincter. METHODS: Invasive needle EMG to assess mean fibre density and neuromuscular jitter was compared directly with quantitative surface EMG in 37 patients with faecal incontinence and 12 age-matched controls. RESULTS: There was a significant positive correlation between mean fibre density on needle EMG and maximum turns rate on surface EMG (rs = 0.48 (95 per cent confidence interval 0.28-0.76), P = 0.003). Furthermore, surface EMG was able to discriminate between patients with normal neuromuscular jitter and those with increased jitter, a measure of progressive denervation and reinnervation, on the basis of reduced rectified mean surface signal (P = 0.02, Fisher's exact test). CONCLUSION: Quantitative surface EMG may potentially replace invasive needle EMG as the investigation of choice in the assessment of anal sphincter electrophysiology.

Anus Diseases↗
PubMed2000

Activation of presynaptic group III metabotropic receptors enhances glutamate release in rat entorhinal cortex.

The role of group III metabotropic glutamate receptors (mGluRs) in modulating excitatory synaptic transmission was investigated in the rat entorhinal cortex (EC) in vitro. AMPA receptor-mediated excitatory postsynaptic currents (EPSCs) were recorded in the whole cell configuration of the patch-clamp technique from visually identified neurons in layers V and II. In layer V, bath application of the specific group III mGluR agonist L(+)-2-amino-4-phosphonobutyric acid (L-AP4, 500 microM) resulted in a marked facilitation of both spontaneous and activity-independent "miniature" (s/mEPSC) event frequency. The facilitatory effect of L-AP4 (100 microM) on sEPSC frequency prevailed in the presence of DL-2-amino-5-phosphonopentanoic acid (100 microM) but was abolished by the group III antagonist (RS)-cyclopropyl-4-phosphonophenylglycine (20 microM). These data confirmed that group III mGluRs, and not N-methyl-D-aspartate (NMDA) receptors were involved in the response to L-AP4. Bath application of the specific mGluR4a agonist (1S,3R,4S)-1-aminocyclopentane-1,2, 4-tricarboxylic acid (20 microM) also had a facilitatory effect on sEPSC frequency, suggesting involvement of mGluR4a. In layer II neurons, L-AP4 caused a reduction in sEPSC frequency but did not affect mEPSCs recorded in the presence of tetrodotoxin. These findings suggest that a group III mGluR with mGluR4a-like pharmacology is involved in modulating synaptic transmission in layer V cells of the EC. The effect on mEPSCs suggests that this receptor is located presynaptically and that its activation results in a direct facilitation of glutamate release. This novel facilitatory effect is specific to layer V and, to our knowledge, is the first report of a direct facilitatory action of group III mGluRs on synaptic transmission. In layer II, L-AP4 had an inhibitory effect on glutamate release similar to that reported in other brain regions.

Aminobutyrates↗
PubMed2000

Cardiac output measured by lithium dilution, thermodilution, and transesophageal Doppler echocardiography in anesthetized horses.

OBJECTIVE: To assess the suitability of lithium dilution as a method for measuring cardiac output in anesthetized horses, compared with thermodilution and transesophageal Doppler echocardiography. ANIMALS: 6 horses (3 Thoroughbreds, 3 crossbreeds). PROCEDURE: Cardiac output was measured in 6 anesthetized horses as lithium dilution cardiac output (LiDCO), thermodilution cardiac output (TDCO), and transesophageal Doppler echocardiographic cardiac output (DopplerCO). For the LiDCO measurements, lithium chloride was administered i.v., and cardiac output was derived from the arterial lithium dilution curve. Sodium nitroprusside, phenylephrine hydrochloride, and dobutamine hydrochloride were used to alter cardiac output. Experiments were divided into 4 periods. During each period, 3 LiDCO measurements, 3 DopplerCO measurements, and 3 sets of 3 TDCO measurements were obtained. RESULTS: 70 comparisons were made between LiDCO, DopplerCO, and triplicate TDCO measurements over a range of 10 to 43 L/min. The mean (+/- SD) of the differences of LiDCO - TDCO was -0.86 +/- 2.80 L/min; LiDCO = -1.90 + 1.05 TDCO (r = 0.94). The mean of the differences of DopplerCO - TDCO was 1.82 +/- 2.67 L/min; DopplerCO = 2.36 + 0.98 TDCO (r = 0.94). The mean of the differences of LiDCO - DopplerCO was -2.68 +/- 3.01 L/min; LiDCO = -2.53 + 0.99 DopplerCO (r = 0.93). CONCLUSIONS AND CLINICAL RELEVANCE: These results indicate that lithium dilution is a suitable method for measuring cardiac output in horses. As well as being accurate, it avoids the need for pulmonary artery catheterization and is quick and safe to use. Monitoring cardiac output during anesthesia in horses may help reduce the high anesthetic mortality in this species.

Animals↗
PubMed1999

Molecular genetic analysis of the Drosophila trithorax-related gene which encodes a novel SET domain protein.

The products of the trithorax and Polycomb groups genes maintain the activity and silence, respectively, of many developmental genes including genes of the homeotic complexes. This transcriptional regulation is likely to involve modification of chromatin structure. Here, we report the cloning and characterization of a new gene, trithorax-related (trr), which shares sequence similarities with members of both the trithorax and Polycomb groups. The trr transcript is 9.6 kb in length and is present throughout development. The TRR protein, as predicted from the nucleotide sequence of the open reading frame, is 2431 amino acids in length and contains a PHD finger-like domain and a SET domain, two highly conserved protein motifs found in several trithorax and Polycomb group proteins, and in modifiers of position effect variegation. TRR is most similar in sequence to the human ALR protein, suggesting that trr is a Drosophila homologue of the ALR. TRR is also highly homologous to Drosophila TRITHORAX protein and to its human homologue, ALL-1/HRX. However, preliminary genetic analysis of a trr null allele suggests that TRR protein may not be involved in regulation of homeotic genes (i.e. not a member of the trithorax or Polycomb groups) or in position effect variegation.

Amino Acid Sequence↗
PubMed1999

Autobiographical memory and dissociation in borderline personality disorder.

BACKGROUND: This study investigated whether individuals with borderline personality disorder (BPD) tend to be overgeneral in their autobiographical recall and whether the extent of their overgeneral recall covaries with their susceptibilities to dissociative experiences, as expected on theoretical grounds. METHODS: Twenty-three patients with BPD and 23 matched controls completed the Autobiographical Memory Test (AMT) and self-report measures of depression, anxiety, trait anger and dissociative experiences. RESULTS: Participants with BPD scored significantly higher than the control group on the measures of depression, anxiety, trait anger, and dissociative experiences and also retrieved significantly more general memories on the AMT. The number of general memories retrieved by the BPD group correlated significantly with their dissociation scores but not with their scores on mood measures. CONCLUSIONS: Patients with BPD have difficulties in recalling specific autobiographical memories. These difficulties are related to their tendency to dissociate and may help them to avoid episodic information that would evoke acutely negative affect.

Adolescent↗
PubMed1999

A physiological barrier distal to the anatomic blood-brain barrier in a model of transvascular delivery.

BACKGROUND AND PURPOSE: Osmotic disruption of the blood-brain barrier (BBB) provides a method for transvascular delivery of therapeutic agents to the brain. The apparent global delivery of viral-sized iron oxide particles to the rat brain after BBB opening as seen on MR images was compared with the cellular and subcellular location and distribution of the particles. METHODS: Two dextran-coated superparamagnetic monocrystalline iron oxide nanoparticle contrast agents, MION and Feridex, were administered intraarterially in rats at 10 mg Fe/kg immediately after osmotic opening of the BBB with hyperosmolar mannitol. After 2 to 24 hours, iron distribution in the brain was evaluated first with MR imaging then by histochemical analysis and electron microscopy to assess perivascular and intracellular distribution. RESULTS: After BBB opening, MR images showed enhancement throughout the disrupted hemisphere for both Feridex and MION. Feridex histochemical staining was found in capillaries of the disrupted hemisphere. Electron microscopy showed that the Feridex particles passed the capillary endothelial cells but did not cross beyond the basement membrane. In contrast, after MION delivery, iron histochemistry was detected within cell bodies in the disrupted hemisphere, and the electron-dense MION core was detected intracellularly and extracellularly in the neuropil. CONCLUSION: MR images showing homogeneous delivery to the brain at the macroscopic level did not indicate delivery at the microscopic level. These data support the presence of a physiological barrier at the basal lamina, analogous to the podocyte in the kidney, distal to the anatomic (tight junction) BBB, which may limit the distribution of some proteins and viral particles after transvascular delivery to the brain.

Animals↗
PubMed1998

A retrospective study of mortality associated with general anaesthesia in horses: emergency procedures.

A retrospective study evaluated 995 emergency equine general anaesthetics. The total mortality for emergency procedures was 31.4 per cent. This figure was examined in more detail to determine if all emergency procedures carried a similar risk. Horses anaesthetised for surgical colic had an increased risk of death or euthanasia, with a total mortality of 35.5 per cent when compared to horses anaesthetised for non-colic related problems which had a total mortality of 15.3 per cent. The findings of this study illustrate the greatly increased risk of mortality in horses undergoing general anaesthesia for emergency procedures. Mortality is 4.25 times more likely for emergency procedures not associated with colic than for similar procedures carried out electively. Emergency general anaesthesia for colic carries an increased risk of mortality of 9.86 times that of elective cases.

Anesthesia, General↗
PubMed1998

A retrospective study of mortality associated with general anaesthesia in horses: elective procedures.

A retrospective analysis examined mortality associated with all procedures requiring general anaesthetic, performed at the Philip Leverhulme Large Animal Teaching Hospital, during the five-year period from February 1991 to December 1995. The study involved details relating to 2276 equine general anaesthetics and a variety of patient variables were examined. Within a group of 1279 animals undergoing anaesthesia for elective procedures, 46 (3.6 per cent) died or were euthanased owing to a poor prognosis or financial implications. Mortality relating directly to the surgery or anaesthesia occurred in eight of these cases. Therefore, the surgical/anaesthetic death rate was 0.63 per cent. Death which was apparently attributable directly to the anaesthesia (no organic cause of death found at postmortem examination) occurred only once, giving an anaesthetic death rate of 0.08 per cent.

Anesthesia, General↗
PubMed1998

The microbiology "unknown" misadventure.

A 19-year-old nursing student was hospitalized after several days of nausea, vomiting, diarrhea, and fevers. Salmonella paratyphi A was isolated from multiple blood cultures. Because this is an unlikely isolate in the United States, an investigation ensued. Two and a half weeks earlier, the student had been working on a microbiology laboratory exercise "unknown." Both the "unknown" organism and the patient's blood culture isolates were identified as S. paratyphi A, with the same biochemical reactions and antimicrobial susceptibility results. The patient's condition improved with antibiotic therapy, and she was discharged after 9 days in the hospital. Conclusions related to our investigation are as follows: (1) relatively virulent organisms were unnecessary to fulfill the laboratory objectives, (2) pipetting by mouth must never be allowed, (3) proper labeling of specimens is imperative, (4) instructors should have knowledge of laboratory safety regulations, and (5) it is the obligation of laboratory directors and administrators to provide a safe academic environment.

Adult↗
PubMed1998

Tachykinins may modify spontaneous epileptiform activity in the rat entorhinal cortex in vitro by activating GABAergic inhibition.

The effects of substance P and related tachykinins on intrinsic membrane properties and synaptic responses of neurons in cortical slices were determined. Substance P had no detectable effect on membrane properties of principal neurons in layer II or V of the rat medial entorhinal cortex or on neurons in either layer of the anterior cingulate cortex. Specific agonists at the neurokinin1-receptor were also without effect as were agonists at both neurokinin1- and neurokinin3-receptors. Substance P hyperpolarized a small number of principal neurons. These responses were weak and desensitized with repeated applications. Similar effects were seen with other neurokinin1-receptor agonists. Excitatory synaptic potentials mediated by either alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate- or N-methyl-D-aspartate-receptors in principal neurons of the entorhinal cortex were unaffected by substance P. Responses of entorhinal neurons to iontophoretically applied glutamate and N-methyl-D-aspartate were also unaffected. Inhibitory synaptic potentials mediated by either GABA(A)- or GABA(B)-receptors in entorhinal neurons were slightly but consistently enhanced by substance P. Neurons identified as interneurons on the basis of their firing characteristics were consistently depolarized by substance P. These responses also desensitized with repeated applications. Spontaneous epileptiform discharges evoked in entorhinal cortex by perfusion with a GABA(A)-receptor antagonist (bicuculline), were reduced in frequency and, sometimes, in duration by substance P. This effect was mimicked by other neurokinin1-receptor agonists and blocked by neurokinin1-receptor antagonists. It was also mimicked by neurokinin A but not by a specific neurokinin1-receptor agonist. The reduction in frequency of discharges was also mimicked by a GABA(B)-receptor agonist, L-baclofen, and blocked by the GABA(B)-receptor antagonist, CGP55845A. Neurokinin B, and a specific neurokinin1-receptor agonist (senktide), increased the frequency and (sometimes) duration of epileptiform discharges. Substance P could also increase frequency but this usually succeeded or preceded a decrease in frequency. The effect of neurokinin B was reduced by a metabotropic glutamate receptor antagonist. Substance P appears to have little direct effect on principal neurons of the entorhinal cortex but may hyperpolarize them indirectly by activating interneurons and releasing GABA. This indirect inhibition may be responsible for the ability of substance P to reduce the frequency of epileptiform discharges in the entorhinal cortex and may suggest that neurokinin1-receptor agonists have potential as anticonvulsant drugs.

Animals↗