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Biomedical subjects

G Clarke

Publications and source records attributed to G Clarke.

At least 109 records · Page 6Linked to original sources

Effect of ACTH on opiate inhibition of oxytocin release.

beta-Endorphin (200ng), dynorphin1-17 (2 micrograms) and morphine (4 micrograms) suppressed the osmotically-evoked release of oxytocin in anaesthetized lactating rats. ACTH1-24 (0.2-3 micrograms) administered intraventricularly 3 min before beta-endorphin or morphine attenuated their inhibitory action, but when applied afterwards was never seen to reverse their effects although this was achieved with naloxone (lmg X kg-1, i.v.). ACTH however, was ineffective against dynorphin. At higher doses an opiate-like action of ACTH was observed. Thus ACTH may act as a partial antagonist and at higher doses as a partial agonist of the opiate receptor for which it is known to have an affinity. It is suggested that suppression of oxytocin release by endogenous beta-endorphin could be modified by ACTH with which it may be co-released.

Adrenocorticotropic Hormone↗

Opioid peptides have differential actions on sub-populations of arcuate neurones.

Extracellular recordings were made from spontaneously active arcuate neurones in hypothalamic slices in vitro. The majority of these neurones (82%) were inhibited in a dose-related manner by opioid peptides added to the perfusion medium at concentrations of 0.1-100 microM. The inhibitory responses were reversed by equimolar concentrations of naloxone. In terms of their latency to 50% inhibition and duration of action the order of potency of the opioid peptides on a molar basis was beta-Endorphin greater than DAGO greater than DADLE greater than Dynorphin. Several sub-populations of arcuate neurones can be identified on the basis of their neuronal activity. Opioid peptides selectively abolished the bursts in those neurones (putative peptidergic neurones) which discharged with a combination of bursts and single irregular action potentials suggesting a selective membrane action rather than an overall hyperpolarizing influence. A population of neurones which displayed episodic or regular activity, and which had action potentials characteristic of dopamine neurones, were profoundly inhibited by the opioid peptides; the activity of a second population of regularly firing neurones with conventional action potential profiles was totally unaffected. These electrophysiological studies thus provide evidence that the arcuate nucleus is one possible site of action at which endogenous opioid peptides could exert their modulatory role on neuroendocrine function; and the predominate influence is likely to be mediated through mu receptors.

Action Potentials↗

Deep vein thrombosis and prostatectomy.

A research protocol to evaluate the prevention of deep vein thrombosis in sequential patients undergoing prostatectomy is presented. There is an overall incidence of deep vein thrombosis in 8 per cent of patients. There was no advantage with intermittent leg compression when compared with elastic stockings.

Clothing↗

Effects of morphine and D-Ala, D-Leu enkephalin on the electrical activity of supraoptic neurosecretory cells in vitro.

Experiments were performed to investigate the effects of morphine and [D-Ala2, D-Leu5]enkephalin on supraoptic cells in hypothalamic slices in vitro. To ensure the presence of a steady background activity, the cells were recorded with glutamate-filled glass microelectrodes and the level of activity was controlled by selecting a suitable retaining current (0.1-9.8 nA). Under these conditions, supraoptic cells showed either the non-phasic (65%) or phasic (35%) firing pattern previously associated with oxytocin or vasopressin cells, respectively. During perifusion of the slice with morphine (10 microM), 10 out of 17 non-phasic supraoptic cells were profoundly inhibited, five cells showed no response and the remaining 2 cells were excited. Similarly with [D-Ala2, D-Leu5]enkephalin (10 microM), 11 out of 15 non-phasic cells were inhibited, 3 cells showed no response and 1 cell was excited. The inhibition produced by morphine or [D-Ala2, D-Leu5]enkephalin could be reversed by concomitant application of naloxone (10 microM). In contrast to the profound effects seen in the non-phasic cells, only 1 out of 13 phasic cells tested with either morphine or [D-Ala2, D-Leu5]enkephalin was inhibited. The remaining 12 phasic cells showed no change in either their overall firing rate or pattern of activity during opiate perifusion. These results provide further evidence that, in addition to their inhibitory effects within the posterior pituitary, opiates can directly suppress the electrical activity of magnocellular neurosecretory cells at the level of the hypothalamus. However, the absence of an opiate effect on the phasic cells might suggest that the action of opioid peptides within the hypothalamus would be exerted predominantly on the oxytocin, rather than the vasopressin cells.

Animals↗

Monoclonal antibody to human eosinophils recognizing 95 kD surface membrane antigen.

Mice were immunized with purified eosinophils obtained from patients with the idiopathic hypereosinophilic syndrome. A hybridoma initially producing an IgM antibody which switched to an IgG1 antibody was selected for cloning and further testing. This IgG1 antibody reacted with human eosinophils, granulocytes, monocytes and large granular lymphocytes, but did not react with T lymphocytes, B lymphocytes, platelets, erythrocytes, or a panel of human leukemia cells and cell lines. Bone marrow analysis revealed staining of myeloid precursor cells but not erythroid precursors or plasma cells. This IgG1 antibody had no effect on aggregation of granulocytes, lysozyme release, superoxide production, chemotaxis, or killing activity; however, there was some stimulation of beta-glucuronidase secretion. While the antibody did not augment the killing of Staphylococcus aureus by granulocytes, the antibody itself was bactericidal. By immunoprecipitation of granulocytes, eosinophils and monocytes, a molecule with a molecular weight of 95 kD was identified.

Animals↗

Determination of the optimal human cell lines for development of human hybridomas.

Six human cell lines were compared with each other and with murine myeloma NS-1 as to their sensitivity to HAT medium and their ability to form hybrids with human lymphocytes, secret monoclonal immunoglobulin, clone, and maintain detectable levels of monoclonal immunoglobulin secretion for a period of time after fusion. Fusion efficiencies varied from 0 to 50%, and the incidence of immunoglobulin secretion ranged between 1 and 78% of the hybrids. Immunoglobulin secretion of cloned hybrids varied from 0.8 to 1.6 micrograms/ml/10(6) cells among the human-human hybrids and was 2.4 micrograms/ml/10(6) cells by the human-mouse hybrid. Among the lines tested, UC729-6 and HF2 appeared optimal for pursuing further studies with human-human hybridomas. In addition, although only a small percentage of hybrids were produced with HMy2, a very high percentage secreted immunoglobulin, so that this line also warrants further investigation to improve the efficiency of hybrid formation. Implications for specific monoclonal antibody production and for therapy of leukemias and lymphomas by anti-idiotype antibodies are discussed.

Animals↗

Silica fragments from millet bran in mucosa surrounding oesophageal tumours in patients in northern China.

Millet bran is a component of the diet in the area of highest oesophageal cancer incidence in northern China. Millet bran was found to contain up to 20% by weight of silica; some of this silica occurs as friable sheets or sharply-pointed fibres. These types of silica in millet bran are the most likely source of an unusual contamination with fragments of silica found in the oesophageal mucosa surrounding tumours in patients in northern China. A group of mucosal samples analysed together contained over 5,000 particles/g (100 parts per million by weight), ten times as many as were found in tissue from normal controls taken at necropsy in London. The modal diameter was 10 microgram (1-70 microgram). The particles were in the body of the mucosa and were not simply a surface contaminant. Silica fragments and fibres of similar size originating from other plant species occur in the diet in the two other regions of greatest incidence of oesophageal cancer, the Transkei and Iran. If such fragments enter the mucosa, they must cause some degree of trauma, and they may also be able to stimulate proliferation by providing anchorage. These findings suggest the possibility that silica particles might be involved in the aetiology of oesophageal cancer.

Adult↗

Pancreatic synthetic rates: a new test of pancreatic function.

Synthesis of pancreatic enzymes was measured in 7 patients with chronic pancreatitis and 10 patients with no pancreatic disease, on the basis of the incorporation of 75Se-methionine into pancreatic exocrine proteins. Two of the patients with chronic pancreatitis had normal exocrine function. Pancreatic secretion was stimulated by intravenous infusion of secretin (1 clinical unit x kg-1 x h-1) and cholecystokinin (1 Ivy dog unit x kg-1 x h-1). 75Se-methionine (3.0 microCi x kg-1) was added to the infusion. Synthetic rates were significantly greater in all the patients with chronic pancreatitis, including the two individuals with normal responses to stimulation with secretin and cholecystokinin. Studies of synthetic rates may therefore be able to confirm the diagnosis of chronic pancreatitis before exocrine insufficiency becomes manifest.

Adolescent↗

Using biofeedback to reduce left arm extensor EMG of string players during musical performance.

Electromyographic (EMG) feedback offers a mechanism for helping musicians reduce specific muscle tension during performance. Nine intermediate to advanced level string players participated in a four-session, pretest/posttest design study to determine (1) if left forearm extensor EMG could be reduced using biofeedback, (2) if reductions in EMG would generalize to a no-feedback condition, and (3) if reductions in EMG would generalize from extensors to flexors. Results indicate that biofeedback did facilitate significant decreases in EMG, that the reductions in EMG did generalize to a no-feedback condition, and that generalization from extensors to flexors did not occur.

Adolescent↗

Evaluation of nystatin stability using tristimulus colorimetry.

A tristimulus reflectance spectrophotometer was used to examine the color changes of nystatin during accelerated stability studies, and a relationship was observed between the loss of microbiological potency and the change in color during thermal degradation. By substitution of the measured tristimulus values in the Kubelka-Munk equation, the remission function was calculated and resulted in a linear response with time. Application of the technique to bulk raw materials and formulated products is demonstrated, and uses of the technique are discussed.

Colorimetry↗

Sleep: a prerequisite for reflex milk ejection in the rat.

Electroencephalographic activity (EEG) was recorded from the frontal cortex of unanaesthetized and urethane-anaesthetized lactating rats and analysed in relation to the pattern of milk ejection evoked by the nursing pups. The EEG of the anaesthetized rat fluctuated without experimental intervention between three distinctive patterns defined as synchronized, desychronized, and stage III activity, whilst reflex milk ejection recurred at intervals of about 6 min (range 2- greater than 20 min) throughout the 1-4 h period the pups were left attached to the nipples. For greater than 10 s before and for up to 60 s after each milk ejection, as judged from recordings of intramammary pressure and pup behaviour, the EEG was invariably synchronized throughout. Conversely, milk ejection (n greater than 300) was never observed during long periods of desynchronized, or stage III EEG activity. The vigorous increase in the sucking of the pups at milk ejection failed to produce a desynchronization (arousal) of the EEG as observed with other forms of sensory stimulation. Indeed, the sucking of the pups appeared to produce a soporific change i, the maternal EEG for spontaneous periods of desynchronization were not observed in the 30-60 min following the initial attachment of the pups to the nipples. Similar EEG patterns were seen in the unanaesthetized rat, though arousal from the synchronized state was more easily produced, e.g., by weak auditory signals. Milk ejection, as judged from the behaviour of the pups, recurred at intervals of 2 min or more during each 20-80 min period of nursing. The rat appeared somnolent for most of the nursing period and the EEG was always synchronized for greater than 10 s before each milk ejection (n greater than 200), though her eyes usually remained open. Arousal and desynchronization of the EEG was invariably observed in association with the increased pup behaviour at milk ejection. From these observations and the knowledge that oxytocin release from the neurohypophysis occurs about 10 s before milk ejection, we conclude that a synchronized EEG pattite for the expression of the milk-ejection reflex in the rat.

Animals↗

Muscular dystrophy in an X; 1 translocation female suggests that Duchenne locus is on X chromosome short arm.

A unique combination of a Duchenne-like muscular dystrophy in a girl with a translocation-inversion rearrangement involving an X chromosome and a no 1 chromosome appeared as a result of both gene mutation and chromosome mutation in the mother. The X-autosome rearrangement would permit full expression of an X-linked recessive gene, such as that for Duchenne muscular dystrophy, in a female, and this would satisfactorily explain the characteristic Duchenne-like course of our patient's illness. The simultaneous de novo appearance of the Duchenne mutation and the X;1 rearrange suggests possible sites for the Duchenne locus on the X chromosome short arm (at Xp1106 or Xp2107).

Child↗

Dopaminergic control of oxytocin release in lactating rats.

During suckling, anaesthetized lactating rats release regular (about every 7 min) but brief pulses of oxytocin (0.5--1.0 mu.) which produce single transient increases in intramammary pressure. Drugs which selectively impair synaptic transmission were used to determine the role of dopamine and noradrenaline in regulating this natural reflex. Diethyldithiocarbamate (100--200 mg/kg, i.v.) and alpha-methylparatyrosine (100--400 mg/kg, i.v.) which inhibit the synthesis of catecholamines both blocked the suckling-induced release of oxytocin. The milk-ejection reflex was also inhibited in a dose-dependent manner by the intravenous administration of the dopamine antagonists, fluphenazine (0.7 mg/kg), pimozide (1.4 mg/kg), cis-dupenthixol (4.5 mg/kg) and metoclopramide (6.0 mg/kg), and caused a significant inhibition P less than 0.01) of the reflex in 50% of the rats tested. The alpha-adrenoceptor antagonist phenoxybenzamine (1.4 mg/kg) was similarly effective. Dopamine (40 micrograms), bromocriptine (10 micrograms), apomorphine (100 micrograms), noradrenaline (10 micrograms) and phenylephrine (2 micrograms) injected into the cerebral ventricles evoked a sustained release of oxytocin which produced multiple increases in intramammary pressure; isoprenaline (4 micrograms) was ineffective. The release of oxytocin evoked by dopamine and noradrenaline was prevented by cis-flupenthixol and phenoxygenzamine respectively. None of the drugs used affected the mammary sensitivity to exogenous oxytocin nor were their actions modified by pretreatment with propranolol (1 mg/kg). The results suggest that the neural pathway for the reflex release of oxytocin during suckling in the rat contains both dopaminergic and noradrenergic synapses, the latter acting through alpha-adrenoceptors and being distal in the pathway to the dopaminergic component.

Amines↗

[Decabromobiphenyl : toxicological study (author's transl)].

The paper presents results of experimental studies on a polybrominated flame retardant. Decabromobiphenyl was found not to be irritant to the rabbit skin or eye. The oral and dermal LD 50' in the rat are greater than 5 g/kg. In a 90 days feeding trial in rats no toxic effect were demonstrated at the levels of 100 and 500 ppm. However, hepatic change occured with diet containing 2.000 ppm. In a 4 weeks dust inhalation study, the no effect level was between 0.005 and 0.05 mg/l of air. The higher concentrations induced hepatic changes. Decabromobiphenyl was not teratogenic or embryotoxic to the rat at 10, 100 and 1.000 mg/kg per os. There was no evidence to indicate that the compound has mutagenic potential. Comparing the toxicological profile of decabromobiphenyl with other polybrominated biphenyl flame retardants would indicate that the toxicity decreases when the number of bromine atoms is increased.

Administration, Oral↗