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J T Williams

Publications and source records attributed to J T Williams.

At least 163 records · Page 9Linked to original sources

Membrane properties of rat locus coeruleus neurones.

Intracellular recordings were made from neurones in the locus coeruleus contained within a slice cut from rat pons and maintained in vitro. Most neurones fired action potentials spontaneously at frequencies of between 1 and 5 Hz; this did not arise from spontaneous synaptic input but appeared to result from endogenous properties of the membrane conductances. Under voltage clamp at potentials near threshold for action potential generation (-55 mV) there was a persistent inward calcium current. This current became less with membrane hyperpolarization and was abolished at about -70 mV. Two potassium currents were observed. The first had properties similar to that generally described as the "fast" potassium current (IK,A); it flowed transiently (for about 200 ms) when the membrane potential passed from about -65 to -45 mV, and was blocked by 4-aminopyridine. The second was a calcium-activated potassium current (IK,Ca); it flowed for several seconds following a burst of calcium action potentials. Spontaneous and evoked action potentials had both tetrodotoxin-sensitive and tetrodotoxin-resistant components. The latter was apparently due to calcium entry. The potential changes occurring during the spontaneous firing of locus coeruleus neurones could be reconstructed qualitatively from the ionic conductances observed. The membrane properties of the locus coeruleus neurones were remarkably uniform; however, about 5% of cells impaled within the region of the locus coeruleus were electrophysiologically distinct. These atypical cells had short duration action potentials, did not fire spontaneously and had large spontaneous depolarizing synaptic potentials.

Action Potentials↗

Opiate-receptor interactions on single locus coeruleus neurones.

Intracellular recordings were made from neurones of the rat locus coeruleus (LC) which were located in a slice of pons superfused in vitro. Opioid agonists and antagonists were applied by adding them to the superfusing solution; normorphine and enkephalin analogues were also applied by ejecting a few nanoliters of a solution which contained the drugs from a pipette situated above the tissue slice. Opioid agonists hyperpolarized LC neurones. This has been shown previously to result from an increase in the membrane potassium conductance. The lowest concentration of normorphine which was effective was 30 nM, the EC50 was 1 microM, and the maximum effect was observed with 30 microM. The irreversible antagonist beta-funaltrexamine (beta-FNA) was used to estimate the dissociation equilibrium constants; these ranged from 9-16 microM for normorphine and [Met5]enkephalin and was about 2 microM for [D-Ala2,D-Leu5]enkephalin. beta-FNA also blocked the hyperpolarization caused by [D-Ala2,D-Leu5]enkephalin, ethylketacyclazocine, and [D-Ser2,D-Leu5] enkephalin-Thr. Naloxone reversibly antagonized the hyperpolarizations caused by normorphine and [D-Ala2,D-Leu5]enkephalin, with a dissociation equilibrium constant of 2 nM. It is suggested that the opioid hyperpolarization of LC neurones is mediated by a receptor having a high affinity for naloxone, previously termed a mu-receptor. The affinity of this receptor for normorphine appears to be 3 to 4 orders or magnitude lower than its affinity for naloxone.

Action Potentials↗

The use of graduated compression stockings in the prevention of postoperative deep vein thrombosis.

The efficacy of graduated compression stockings in the prevention of postoperative deep vein thrombosis was studied in a randomized, prospective, controlled trial of 200 patients, aged 40 years and over, undergoing abdominal surgery (100 for benign disease, 100 for malignant conditions). Deep vein thrombosis was diagnosed by the 125I-fibrinogen test. The incidence of deep vein thrombosis was 35.9 per cent in the control group (103 patients) and 15.5 per cent in the stockinged group (97 patients) (P less than 0.025). In the patients with benign disease, deep vein thrombosis developed in 24.5 per cent of the control limbs and 6.1 per cent of stockinged limbs (P less than 0.005); in patients with malignant disease the similar figures were 27.9 and 11.5 per cent (P less than 0.05). Increasing age did not alter the efficacy of the stockings. It is concluded that graduated compression stockings provide a safe and effective method of prophylaxis against deep vein thrombosis.

Abdomen↗

Opiate activation of potassium conductance inhibits calcium action potentials in rat locus coeruleus neurones.

Opiates act on mu-receptors to increase the potassium conductance of rat locus coeruleus neurones. Opiates also depress the rate of rise and peak amplitude of calcium action potentials in these cells. The action of opiates on calcium action potentials was prevented by two procedures which blocked the opiate-induced potassium current, intracellular caesium and extracellular barium. This indicates that the opiate reduction in calcium entry is secondary to an increased potassium current.

Action Potentials↗

Noradrenaline-mediated synaptic inhibition in rat locus coeruleus neurones.

Intracellular recordings were made from neurones in the nucleus locus coeruleus (l.c.) in slices of rat pons maintained in vitro. Focal electrical stimulation to the slice surface within the region of the l.c. evoked a synaptic depolarization followed by a hyperpolarization. These potentials were graded with stimulus intensity and were abolished in calcium-free and/or high-magnesium solutions. The nature of the hyperpolarizing synaptic potential (i.p.s.p.) was investigated. The i.p.s.p. amplitude decreased as the membrane was artificially made more negative and reversed at -114 mV. This reversal potential shifted to less negative potentials in solutions of elevated potassium ion content as predicted by the Nernst equation. The i.p.s.p. was potentiated in amplitude and its time course was prolonged by desmethylimipramine (DMI). Yohimbine (100 nM) and phentolamine (100 nM) reversibly abolished the i.p.s.p. and did not change the synaptic depolarization. Noradrenaline hyperpolarized all l.c. neurones tested, whether applied by perfusion (1-30 microM) or by pressure ejection from a micropipette placed in the solution near the recording site. The noradrenaline-induced hyperpolarization was accompanied by an increase in conductance and it reversed in polarity at -104 mV. The reversal potential of the noradrenaline hyperpolarization became less negative when the potassium ion content was increased. The noradrenaline-induced hyperpolarization was potentiated by DMI and was antagonized by yohimbine and phentolamine in the same concentrations which blocked the i.p.s.p. The results support the notion that l.c. neurones can release noradrenaline onto the somadendritic membrane of other l.c. neurones and thereby provide local feed-back inhibition.

Action Potentials↗

The acute effects of capsaicin on rat primary afferents and spinal neurons.

Capsaicin applied to the soma of fast and slow conducting primary afferent fibers had a depolarizing action associated with an increase in membrane conductance. The depolarizing effect desensitized rapidly and was only partially reversible in slow conducting fibers. Capsaicin application to the entry zone of the appropriate dorsal rootlets led to strong excitation of dorsal horn neurons receiving multimodal input. After acute capsaicin treatment the response to noxious heat was attenuated or totally absent, while other noxious stimuli were still effective. The present data suggest that capsaicin exerts its specific degenerative action by a long-lasting depolarizing action on small-calibre fibers.

Afferent Pathways↗

Diabetic gangrene in black patients.

We reviewed diabetic gangrene in 104 American blacks and found that the clinical features were similar to those reported for the general diabetic population. We observed, however, that there was a significant association of hypertension with above-knee and bilateral amputations in our patients (P less than .001 and .01, respectively), and that the mean blood pressure of the bilateral amputees (124.5 +/- 3.8 mm Hg) (SEM) was significantly higher (P less than .005) than that of the unilateral amputees (114.4 +/- 1.7 mm Hg). There results suggest a strong association of hypertension with far-advanced occlusive vascular disease of the lower limbs. Moderately severe anemia (hematocrit 20% to 30%) was associated significantly with primary above-knee amputation and mortality (P less than .02 and .05, respectively). Mortality resulted mostly from mixed causes (cardiopulmonary failure, uremia, sepsis, diabetic coma). The dead patients had significantly increased prevalence of cardiac disease (P less than .02), higher frequency of above-knee amputation (P less than .01), and a duration of diabetes (17.4 +/- 2.8 years) significantly longer (P less than .025) than that of the surviving patients (12.0 +/- 1.0 years).

Adult↗

Neurons in the frontal cortex of the rat carry multiple opiate receptors.

Acute desensitization to the inhibitory action of iontophoretically applied opiate alkaloids and opioid peptides was used to investigate the possibility of multiple opiate receptors located on single neurons in the frontal cortex of rats. Such short term exposure resulted in adaptive processes which were similar to tolerance to and dependence on opiate agonists occurring after chronic treatment. Neurons desensitized to methionine-enkephalin (ME) or D-Ala2,D-Leu5-enkephalin (DADL) became subsensitive to morphine, whereas cells desensitized to morphine remain sensitive to the inhibitory action of the opioid peptides. This lack of cross-desensitization may suggest the existence of multiple opiate receptors on the same cell.

Animals↗

Value of outpatient follow-up after curative surgery for carcinoma of the large bowel.

The records were reviewed of 406 patients with carcinoma of the large bowel who had been treated at the Middlesex Hospital during 1958-62. Of these patients, 180 were followed up regularly in this hospital after radical surgery, and from six months to 15 years after operation they were seen 2319 times; 71 developed a recurrent carcinoma but, of these, 41 recurrences (58%) were diagnosed at times other than those of the patients' routine outpatient appointments, although they were being regularly reviewed. Only one patient with recurrence appeared to have been cured by further surgery. For the present, adequate education of patients in the symptoms of early recurrence, with instruction to return if any of these develop, is likely to be more effective than the unsatisfactory and time-consuming routine follow-up still used in many hospitals.

Anus Neoplasms↗

A prospective study of sexual function after major colorectal surgery.

Excision of the recto-sigmoid and rectum for cancer or inflammatory disease frequently damages the autonomic nerve supply. The anatomy and function of the autonomic nervous system in the pelvis is reviewed. Thirty-two patients who underwent excision of the rectum have been studied: 28 operations were for carcinoma, 4 for ulcerative colitis. A detailed history of sexual function was obtained preoperatively together with a neurological examination of the genitalia and perineum. Biopsies were taken from the surgical specimens and examined for the presence of nerve tissue. A further sexual history was taken 3 months postoperatively. Ten sexual active men (ages 46-74) who had anterior resections or abdominoperineal excisions for carcinoma tended to show impaired sexual activity if there was excessive nerve tissue in the specimen. Two out of 3 sexually active women (ages 53-68) who had cancer operations had satisfactory sexual function postoperatively. Four patients (ages-66) all had satisfactory sexual function after panproctocolectomy for ulcerative colitis. The advantages of avoiding damages to the pelvic autonomic nerves at operation are discussed.

Adult↗

The action of substance P on neurons of the myenteric plexus of the guinea-pig small intestine.

Extracellular and intracellular recordings were made in vitro from single neurons of the myenteric plexus of the guinea-pig small intestine. Synthetic substance P was applied to the neurons by means of the perfusing solution or by electrophoresis from micropipettes. Extracellular recording showed that substance P (100 pm-30 nm), applied by perfusion, increased the firing rate of myenteric neurons. Intracellular recording indicated that perfusion with substance P caused a dose-dependent membrane depolarization which was unaffected by hexamethonium, hyoscine, naloxone or baclofen. The depolarization was also evoked by electrophoretic application of substance P. It was associated with an increase in membrane resistance, augmented by membrane depolarization and reduced by membrane hyperpolarization. The relation between the substance P reversal potential and the logarithm of the extracellular potassium concentration was linear with a slope of 54 mV/log10[K+], which indicates that substance P inactivates the resting potassium conductance of the myenteric neurons. This effect on ion conductance is the same as that of an unknown substance that mediates slow synaptic excitations with the myenteric plexus.

Action Potentials↗

The action of neurotensin on single myenteric neurones.

The action of neurotensin was studied on single myenteric neurones within ganglia of the myenteric plexus isolated from the guinea-pig ileum. Drugs were applied by adding them to the perfusing Krebs solution. Extracellular recording with glass suction electrodes indicated that neurotensin (100 pM-300 nM) caused a dose-dependent excitation of about 50% of myenteric neurones; the remaining neurones were unaffected. This effect persisted in calcium-free solutions. Intracellular recording showed that a similar proportion of Type 1 myenteric neurones were depolarized by neurotensin: this was associated with an increase in membrane resistance. Type 2 cells were either depolarized or hyperpolarized by neurotensin. The depolarization persisted in calcium-free solutions. The hyperpolarization disappeared in calcium-free solutions, suggesting either that the potential change itself is calcium-dependent or that it was due to release by neurotensin of a hyperpolarizing substance.

Animals↗

Effects of endorphins on single myenteric neurons.

Methionine-enkephalin, leucine-enkephalin and beta-endorphin were applied in known concentrations to an in vitro preparation of myenteric neurons from the guinea-pig ileum. All 3 substances caused a rapid, reversible and dose related inhibition of the firing of myenteric neurons induced and recorded with extracellular suction electrodes. This inhibition of firing occurred at low agonist concentrations (1-300 nM) and was reversed by naloxone and a benzomorphan narcotic antagonist. The inhibition persisted in solutions which were completely free of calcium ions -- thus indicating that the observed effect is taking place directly on the neuron from which the recording is made, and that calcium ions are not required for this inhibitory action of endorphins on neuronal firing.

Animals↗