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D Johnston

Publications and source records attributed to D Johnston.

At least 253 records · Page 14Linked to original sources
PubMed1990

Induction of long-term potentiation at hippocampal mossy-fiber synapses follows a Hebbian rule.

1. The induction of long-term potentiation (LTP) at hippocampal mossy-fiber synapses requires an increase in postsynaptic [Ca2+]i but is independent of N-methyl-D-aspartate (NMDA) receptor activation. Voltage-gated Ca2+ channels have been proposed as one alternative source for raising [Ca2+]i during the induction of LTP. We tested the hypothesis that voltage-gated Ca2+ channel activation could mediate the induction of LTP by examining whether 1) the induction of mossy-fiber LTP was dependent on postsynaptic depolarization and 2) depolarization alone, of a magnitude presumably capable of activating Ca2+ channels, was sufficient to induce LTP. 2. Intracellular recordings were made from rat CA3 pyramidal cells in the hippocampal slice preparation under both current- and voltage-clamp conditions. Mossy-fiber postsynaptic potentials and currents were recorded before and after high-frequency stimulation (HFS) in the presence of 20-50 microM D-2-amino-5-phosphonovaleric acid (D-APV), an NMDA-receptor antagonist. 3. Voltage clamping of CA3 neurons between -80 and -100 mV during HFS reversibly blocked the induction of mossy-fiber LTP. Conversely, HFS paired with depolarizing-current steps under current clamp increased the magnitude of LTP compared with controls. These results indicate that mossy-fiber LTP is dependent on postsynaptic depolarization, and presynaptic activation alone was not sufficient to induce mossy-fiber LTP. 4. Depolarizing-current injections, which presumably depolarized CA3 cells to potentials sufficient to activate voltage-gated Ca2+ channels, had no effect on mossy-fiber synaptic responses. These results suggest that synaptic activation, in addition to postsynaptic depolarization, is required for the induction of mossy-fiber LTP. 5. Single mossy-fiber afferent volleys were also paired with depolarizing-current pulses. In the presence of APV, pairing of single-mossy-fiber excitatory postsynaptic potentials (EPSPs) with postsynaptic depolarization did not potentiate synaptic responses, suggesting that some form of HFS is also required for mossy-fiber LTP. In the absence of APV, however, the contamination of mossy-fiber synaptic responses by CA3-recurrent inputs resulted in some potentiation. 6. These results suggest that the induction of mossy-fiber LTP is dependent on both pre- and postsynaptic activity and thus follows a Hebbian rule for synaptic modification. In contrast to that demonstrated at Schaffer-collateral-commissural synapses, however, the induction of mossy-fiber LTP may require HFS in addition to postsynaptic depolarization.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

Epileptiform activity in the hippocampus produced by tetraethylammonium.

1. The epileptiform discharges in the CA3 region of the rat hippocampal slice produced by bath application of the potassium channel blocker tetraethylammonium (TEA) were investigated. The effects of a convulsant (5 mM) and subconvulsant (0.5 mM) concentration of TEA on the mossy fiber-evoked synaptic currents were studied by the use of voltage-clamp techniques to determine whether TEA, like 4-aminopyridine (4-AP), another potassium channel blocker and convulsant, increased both inhibitory and excitatory components of the synaptic response. 2. At extracellular potassium concentrations of 2.5 mM, TEA (5 mM) was found to produce spontaneously occurring epileptiform discharges that could be recorded extracellularly. The intracellular correlate of the epileptiform discharge, the paroxysmal depolarizing shift (PDS), could be reversed in polarity by depolarizing the membrane and was associated with a large increase in membrane conductance. These results suggest that a synaptically mediated potential underlies the generation of the epileptiform discharge. 3. The reversal potential for the PDS was dependent on the time, relative to the extracellularly recorded field discharge, at which the measurement was made. In current clamp the mean reversal potential of the PDS measured at the midpoint of the extracellular discharge was -3.3 +/- 2.9 (SE) mV (n = 9). The reversal potential of the PDS was considerably more negative when measured either before or after the midpoint of the extracellular discharge, suggesting the presence of an inhibitory synaptic component. In voltage clamp similar results were obtained and a large conductance change was found to be associated with the PDS. These results suggest that the synaptic conductance associated with the PDS has both inhibitory and excitatory components. 4. TEA increased significantly the mossy fiber-evoked, early-inhibitory conductance. A convulsant concentration (5 mM) increased the conductance measured 15 ms after the stimulus from 39.7 +/- 8.7 to 87.2 +/- 8.0 nS (n = 6). The reversal potential associated with the conductance depolarized from -68.3 +/- 3.4 to -58.3 +/- 4.0 mV after 5 mM TEA. A subconvulsant concentration of TEA (0.5 mM) also increased the conductance of the mossy fiber-evoked response at 15 ms after the stimulus from 49.5 +/- 3.1 to 63.1 +/- 6.1 nS (n = 4) without an associated shift in reversal potential. 5. The late-inhibitory component of the mossy fiber-evoked response, when present, was increased by 5 mM TEA and unchanged by 0.5 mM TEA. 6. The excitatory mossy fiber-evoked synaptic current was studied in the presence of picrotoxin and was found to be increased and prolonged by 5 mM TEA.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

Muscarinic depression of synaptic transmission at the hippocampal mossy fiber synapse.

1. The action of muscarine was studied in the CA3 region of the rat hippocampal slice with single-electrode voltage-clamp techniques. 2. Bath application of 1 or 10 microM muscarine produced an increase in the input resistance of these cells and reduced the slow afterhyperpolarization (sAHP) response. Changes in input resistance were more pronounced around the resting potential of the cell (-50 to -60 mV), but in many cells an effect was also seen at -80 mV. These effects were absent when cesium chloride-containing microelectrodes were used. 3. At 1 microM, muscarine had little effect on synaptic transmission, causing a 0 +/- 7% (mean +/- SE, n = 19) change in excitatory postsynaptic potential (EPSP) and decreasing the excitatory postsynaptic current (EPSC) by 11 +/- 6% (n = 14); neither change was statistically significant. 4. In contrast, 10 microM muscarine produced a reliable depression of both the EPSP and EPSC. This effect was independent of the electrolyte used: with KCl the EPSP was depressed 23 +/- 4% (n = 5) and the EPSC 35 +/- 5% (n = 4); for CsCl the EPSP was depressed 23 +/- 10% (n = 7) and the EPSC 34 +/- 5% (n = 7). 5. Muscarine did not alter the reversal potential of the synaptic current but merely produced a decrease in slope conductance (37 +/- 5%, n = 6). 6. Muscarine did not significantly alter the shape of the EPSC waveform. This was assessed by comparing the 10-90% rise time and the half decay time of the current before and after muscarine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Differential modulation of single voltage-gated calcium channels by cholinergic and adrenergic agonists in adult hippocampal neurons.

1. Pharmacologic agents known to modulate long-term potentiation (LTP) at the mossy fiber-to-CA3 pyramidal neuron synapse were tested for their effects on the activity of single voltage-gated calcium channels in adult CA3 pyramidal neurons. 2. Single-channel current recordings of three types of voltage-gated calcium channels were made from acutely exposed CA3 pyramidal neurons of the adult guinea pig hippocampus. 3. The beta-adrenergic agonist isoproterenol (10 microM), which is known to enhance LTP, increased the activity of the two high-threshold calcium channels (N and L) with no striking effect on the low-threshold (T) channel. 4. The muscarinic agonists carbachol and muscarine (1-10 microM), the latter of which has been shown to inhibit LTP, decreased the probability of opening of L channels, increased the probability of opening of T channels, and had no effect on N channels. The effects were blocked by 0.1 microM atropine. 5. These results are consistent with the hypothesis that neuromodulation of mossy fiber LTP occurs, at least in part, through the modulation of postsynaptic, voltage-gated calcium channels.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1990

The effects of 15 days of dosing with placebo, sufotidine 600 mg nocte or sufotidine 600 mg twice daily upon 24-hour intragastric acidity and 24-hour plasma gastrin.

The acid inhibitory effect of sufotidine, a potent, long-lasting, competitive H2-receptor antagonist, was studied in 12 healthy males in a double-blind, randomized, three-way cross-over study of the effect of placebo, sufotidine 600 mg nocte and sufotidine 600 mg b.d. given over 15 days. On day 1 and 15 of dosing with each regimen, each subject's 24-h ambulatory intragastric acidity was measured by radiotelemetry and 24-h plasma gastrin profiles were derived from hourly venous blood samples. Acid suppression was calculated as the decrease in the area under the curve of hydrogen ion activity vs time from that observed on placebo, and 24-h plasma gastrin calculated as the area under the curve of plasma gastrin concentration vs time. Twenty-four hour intragastric acidity during the fifteenth day of dosing with sufotidine 600 mg nocte and sufotidine 600 mg b.d. did not differ significantly, but on the first and fifteenth day of dosing nocturnal acidity was decreased to a greater extent by sufotidine 600 mg nocte than sufotidine 600 mg b.d. (P less than 0.005). After 15 days, the acid suppression afforded by sufotidine 600 mg b.d. was significantly attenuated (P less than 0.0005); this was associated with a rise in 24-h plasma gastrin (P less than 0.001). Thus, tolerance to the acid inhibitory effect of H2-receptor antagonists exists and is of rapid onset. We suggest that tolerance is mediated by the temporally associated rise in 24-h plasma gastrin, but we cannot exclude the possibility that other mechanisms, such as up-regulation of H2-receptors, also play a part.

Adult↗
PubMed1990

Fatal right ventricular thrombus secondary to Hickman catheterisation.

Complications arising from central venous cannulation include sepsis, thrombosis and trauma. Total parenteral nutrition via a Hickman catheter is an accepted therapeutic technique. Cases of catheter-related thrombus within the right atrium have been described, primarily in premature infants, although a recent case has been reported in an adult. We describe the presence of a fatal right ventricular thrombus in a female with an infected Hickman catheter.

Adolescent↗
PubMed1990

Pelvic haemophilic pseudotumour occurring in a patient with mild haemophilia: a brief report.

Haemophilic pseudotumour is a rare but well-recognized complication of moderate and severe haemophilia, particularly in patients who have developed a factor VIII inhibitor. It has only been reported in haemophiliacs with factor VIII or IX levels less than 5%. We report a patient with mild haemophilia (factor VIII 11%, factor IX 78%) who developed a pelvic pseudotumour that was successfully treated with a novel surgical technique and who has no evidence of recurrence five years after operation.

Fistula↗
PubMed1989

Somatostatin analogue SMS 201-995 (octreotide) as a possible solution to the dumping syndrome after gastrectomy or vagotomy.

The dumping syndrome, which may follow partial gastrectomy or truncal vagotomy and drainage, may be refractory to treatment. The aim of this study was to determine the effect of the somatostatin analogue, SMS 201-995 (octreotide), on dumping provoked by hypertonic glucose. Ten patients with symptoms and signs of dumping were studied. After a dumping provocation test with placebo, all patients developed severe symptoms: seven patients had early dumping, two had both early and late dumping and one had late dumping alone. With either 50 or 100 micrograms SMS 201-995, the symptoms of early dumping were much reduced in all patients, and those of late dumping were completely abolished. The packed cell volume, pulse and systolic blood pressure changes of early dumping were significantly reduced by SMS 201-995 and the fall in blood glucose in patients with late dumping was abolished. SMS 201-995 may be a useful treatment for early and late dumping.

Adult↗
PubMed1989

Comparison of histopathological and flow cytometric parameters in prediction of prognosis in gastric cancer.

Flow cytometric analysis was performed retrospectively on material from 76 patients having potentially curative resection for gastric carcinoma between 1968 and 1984. The prognostic significance of DNA aneuploidy was compared with that of conventional histological grading and staging of the tumour. The presence of DNA aneuploidy was associated with a significantly poorer prognosis when compared with diploid tumours (P less than 0.02), but was not found to be predictive of survival when the presence of lymph node metastases (P less than 0.0001) and resection margin involvement (P less than 0.003) were allowed for using multiple regression analysis. When intestinal and diffuse types of gastric carcinoma were analysed separately, DNA aneuploidy was associated with a significantly shorter survival only in patients with intestinal type tumours.

Adult↗
PubMed1989

Preservation of ileocecal junction and entire anal canal in surgery for ulcerative colitis--a "two-sphincter" operation.

Disruption of the terminal ileum and excision of the ileocecal junction during restorative proctocolectomy and formation of a pelvic ileal reservoir may lead to abnormalities of motility, transit, and absorption. We therefore preserved this portion of the gastrointestinal tract in 12 patients who underwent restorative proctocolectomy for ulcerative colitis. In each patient, the entire anal sphincter was preserved without mucosal stripping: the two sphincters were connected by a single loop of ileum without any reservoir. After median follow-up of 12 months, the functional results were similar to those seen with conventional pelvic ileal reservoirs and superior to the results of mucosal proctectomy and straight endoanal ileoanal anastomosis. This operation may be an alternative to standard restorative proctocolectomy for patients with ulcerative colitis.

Adolescent↗
PubMed1989

Changes in the absorption of bile acids after total colectomy in patients with an ileostomy or pouch-anal anastomosis.

Bile acid absorption was investigated using 75Se Taurohomocholate (SeHCAT) in controls and patients who had undergone total colectomy with either conventional ileostomy or pouch-anal anastomosis for ulcerative colitis or adenomatous polyposis. Whole-body retention of SeHCAT after 168 hours was greater in the controls than the patients who had undergone colectomy (P less than .05). Retention of SeHCAT did not differ significantly between patients with an ileostomy and patients with pouch-anal anastomosis, but patients with an ileostomy and ileal resection of more than 20 cm retained less SeHCAT than patients with a pouch-anal anastomosis (P less than .01). Analysis of fecal bile acids from ileostomies and pouches showed that bacterial metabolism of primary conjugated bile acids was greater in patients with a pouch. It was concluded that bile acid absorption was not significantly impaired by construction of a pouch compared with conventional ileostomy, but bacterial metabolism of bile acids was greater in the pouches.

Adolescent↗
PubMed1989

Long-term potentiation of hippocampal mossy fiber synapses is blocked by postsynaptic injection of calcium chelators.

The role of intracellular calcium in an APV-insensitive form of long-term potentiation (LTP) has been studied at the hippocampal mossy fiber synapse. Intracellular calcium was buffered by iontophoretic injection of either BAPTA or QUIN-2, into CA3 pyramidal neurons. The slow calcium-dependent after hyperpolarization was used as an indicator of buffering. LTP was elicited in control and in APV-treated cells (6/6 and 4/5 cell, respectively). In contrast, LTP was observed in only 2/9 BAPTA-loaded cells and in 1/4 QUIN-2-loaded cells. The magnitude of LTP for control and APV-treated cells were not significantly different, but both groups showed significantly greater LTP than BAPTA-loaded cells. These results suggest that an increase in postsynaptic calcium is required for the induction of mossy fiber LTP.

2-Amino-5-phosphonovalerate↗
PubMed1989

The effects of old age and immobility on protein turnover in human subjects with some observations on the possible role of hormones.

Protein turnover (PT), synthesis (PS) and breakdown (PB) were studied using L-(1-14C)-leucine and primed continuous infusion of 14C-HCO3 over a 6-h study period in three groups: group 1 (n = 9) fit old; group 2 (n = 6) fit young; and group 3 (n = 13) immobile old. Plasma cortisol, growth hormone (GH) and insulin levels were measured during the studies. There were significant reductions in PT (p less than 0.02), PB (p less than 0.02) and PS (p less than 0.01) in fit old compared to fit young subjects. Comparison between fit old versus immobile old subjects revealed that the immobile group (Group 3) had higher PT (p less than 0.05), PB (p less than 0.05) and PS (p less than 0.01) rates. The rates of protein turnover and components in group 3 were similar to those in group 2. There was greater variance in protein balance in the immobile subjects. Significantly higher plasma cortisols were found in the immobile than in the healthy old subjects. The immobile group had higher GH levels in response to feeding but there was no difference in insulin response to feeding. These higher plasma cortisol and GH levels may be partly responsible for the changes in PT found in immobile elderly patients.

Aged↗
PubMed1989

Immunogenicity and tumor protective activity of B16 melanoma vaccines.

The immunogenicity and tumor-protective activity of different vaccines were examined and compared with murine B16 melanoma. All vaccines were prepared from material shed into culture medium by B16 melanoma cells. Vaccine I was generated by concentrating the shed material. Vaccine II was partially purified by precipitating the shed material with 50% ammonium sulfate followed by sephadex G-200 column chromatography. Vaccine III was concentrated shed material that was treated with 0.5% NP-40 and then ultracentrifuged to remove transplantation antigens. Mice were immunized to equal protein concentrations of vaccines weekly for 5 weeks or to control buffer. Antibody, cellular, and tumor-protective immunity to melanoma was measured in all mice 2 weeks following the last immunization. All three vaccine preparations were immunogenic. Vaccine preparation I appeared to be the most immunogenic and the one that most consistently augmented tumor-protective immunity. Augmentation in tumor-protective immunity correlated better with increase in cellular than in humoral immunity to melanoma.

Animals↗
PubMed1989

Ileal ecology after pouch-anal anastomosis or ileostomy. A study of mucosal morphology, fecal bacteriology, fecal volatile fatty acids, and their interrelationship.

Ileal mucosal morphology, fecal bacteriology, fecal volatile fatty acids, and their interrelationships were studied in 15 patients with an ileal pouch-anal anastomosis and 14 patients with an ileostomy after proctocolectomy for ulcerative colitis. Pouch effluent, compared with ileostomy effluent, had a greater ratio of anaerobes to aerobes (p less than 0.05), and greater numbers of Bacteroides (p less than 0.01) and Bifidobacteria (p less than 0.05). Fecal volatile fatty acids, products of anaerobic bacterial fermentation, were also increased in pouch effluent compared with ileostomy effluent (propionate, p less than 0.05; butyrate, p less than 0.01). Mucosal change in the pouches showed no significant correlation with frequency of defecation, completeness of emptying, or pouch design, but the degree of villous atrophy was correlated with the number of Bacteroides (rs = 0.93, p less than 0.01) and with fecal butyrate (rs = 0.68, p less than 0.05). Fecal propionate was significantly correlated with the percentage of stool retained after defecation (rs = 0.82, p less than 0.01). These findings indicate that the bacterial ecology of ileal pouches has an important influence on the morphology of their mucosal lining.

Adult↗
PubMed1988

Nucleic acid flow cytometry in large cell lymphoma.

Between 1978 and 1985, 140 patients with large cell lymphoma (27 follicular, 92 diffuse, 5 immunoblastic, and 16 transformed) had DNA-RNA cytometry performed on involved tissue. DNA-RNA features were correlated with treatment outcome and compared to other established prognostic factors in 63 newly diagnosed patients who received uniformly intensive therapy. Significantly better outcome was noted for previously untreated patients with intermediate RNA content (RNA index, 1.0-1.8), diploid DNA content, and (during the initial 12-month follow-up) low proliferative activity. Of patients followed beyond 12-24 months, those with high proliferative activity appeared to have the most durable remissions, although this was not statistically significant. These findings suggested a preferential impact of intensive chemotherapy on patients with intermediate RNA content and possibly those with high proliferative activity, since previous studies and our own experience with relapsing patients have indicated a progressively worse outlook with higher proliferative activity and RNA index values. In newly diagnosed patients, multivariate analysis identified RNA content as the most important prognostic factor, followed by proliferative activity and serum lactate dehydrogenase. Thus, for patients with large cell lymphoma, DNA-RNA cytometry appears to be a valuable prognostic parameter for identifying a subset of patients who have a high likelihood of cure with intensive chemotherapy.

Analysis of Variance↗