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Biomedical subjects

M Wilkinson

Publications and source records attributed to M Wilkinson.

At least 235 records · Page 13Linked to original sources
PubMed1986

Association of diurnal variations in hypothalamic but not cortical opiate ([3H]-naloxone)-binding sites with the ability of naloxone to induce LH release in the prepubertal female rat.

We report the existence of a diurnal variation in the binding of the opiate antagonist [3H]-naloxone to slices of the mediobasal hypothalamus from prepubertal female rats. The binding is highest in the early morning and reaches a nadir in the late afternoon. Opiate binding in cortical slices from such animals is constant over the course of the day. Changes in receptor density, and not in receptor affinity, account for the diurnal variation in the amount of ligand bound. These diurnal variations in receptor numbers are associated with changes in the ability of naloxone to release LH and may be crucial in the transition from the juvenile state to one of competent reproductive functioning.

Animals↗
PubMed1986

Epidermal growth factor causes hypocalcemia in sheep.

During iv infusions of epidermal growth factor into sheep, serum calcium concentrations fell, whereas serum magnesium and serum immunoreactive PTH levels increased. Urinary calcium and magnesium decreased significantly. The role of epidermal growth factor in calcium homeostasis is discussed.

Animals↗
PubMed1985

Interferon gamma produced by mitogen-activated T lymphocytes does not directly mediate lymphoproliferation.

Human interferon gamma (IFN-gamma) endogenously produced during mitogenic stimulation of human peripheral blood mononuclear cells or human T lymphocyte-enriched cultures was neutralized in situ by the addition of a polyclonal antiserum (anti-L) raised in a rabbit against partially purified natural IFN-gamma derived from peripheral blood mononuclear cells. Small decreases in mitogen-induced [3H]thymidine incorporation (lymphoproliferation) were demonstrated under these conditions. However, an antiserum (anti-G) raised in a sheep against highly purified recombinant IFN-gamma (E. coli-derived) which strongly neutralized the antiviral effect of IFN-gamma either had little effect on mitogen-induced lymphoproliferation or caused slight enhancement of mitogenesis. The interleukin 2 responsiveness of activated T lymphocytes following mitogenic stimulation was not found to be different in the presence of anti-G to that of control cultures incubated in the presence of normal sheep serum. These results suggest that IFN-gamma is not a direct requirement for lymphoproliferation.

Antibodies↗
PubMed1985

Direct effects of the adrenergic neurotoxin DSP4 on central opiate receptors: implications for neuroendocrine studies.

We have shown that the noradrenergic neurotoxin DSP4 can acutely abolish naloxone-induced secretion of LH in the rat. A part of this influence is clearly related to an unexpected interaction with hypothalamic opiate ( [3H]-naloxone) binding sites. Injection of DSP4 (50 mg/kg) can severely reduce opiate binding assayed in vitro. In addition, the drug is very potent in blocking opiate receptors in vitro, as determined in slice and homogenate assays. Consideration must now be given to the possibility that many previous studies on acute effects of DSP4 undoubtedly involved the opiatergic system in addition to noradrenergic terminals. Thus, DSP4 is not the drug of choice for experiments designed to probe catecholamine-opiate interactions in the control of LH release.

Amines↗
PubMed1985

Beta-adrenergic [( 3H]CGP-12177) binding to brain slices and single intact pineal glands.

We have characterized and quantified the binding of [3H]CGP-12177 to beta-adrenergic receptor sites in slices (300 microns) of rat cerebral cortex. The receptors are stereospecific, saturable and of high affinity. Binding of [3H]CGP is readily reversible and demonstrates appropriate drug specificity. This assay method allows the demonstration of isoproterenol-induced down-regulation (internalization) of beta-adrenoreceptors. Receptor recycling is observed at 37 degrees C in the absence of beta-agonist but can be blocked by low temperature (0 degree C) or by monensin. beta-Adrenoreceptors can also be labeled and quantified in intact, single pineal glands of rat, mouse and hamster. Rat pineals contain approximately 10 times more binding sites than do hamster or mouse pineals and up to 8 times more sites than found in rat cerebral cortex. Rat pineal [3H]CGP binding can be up- and down-regulated but not to the same degree as seen in brain slices. This assay method is simple, rapid and provides new opportunities for the study of other receptor types in intact tissue.

Adrenergic beta-Antagonists↗
PubMed1985

Modification of neurotransmitter receptor sensitivity in cat visual cortex during the critical period.

We have examined the characteristics of various receptors in cat visual cortex during postnatal development. These included beta-adrenergic, GABA, benzodiazepine and acetylcholine receptors. For each population of receptor the number (Bmax) and affinity (Kd) were examined as a function of postnatal age (3 days-adult). For all receptors examined, the Bmax increased during development from low early values to a peak within the critical period. The Kd also changed during development for most receptors. The simultaneous alterations in Bmax and Kd necessitate defining a term which takes both of these receptor properties into consideration. This term, called receptor sensitivity (RS), provides a more comprehensive measure of receptor function than either Bmax or Kd alone. Using this measure, we find that receptor sensitivity is low near birth for the 4 receptor populations studied, rises to a peak within the first two months of life, and then declines to near-neonatal levels for 3 of the 4 receptor populations.

Animals↗
PubMed1985

The noradrenergic neurotoxins DSP4 and xylamine bind to opiate receptors.

DSP4 and xylamine compete with [3H]-naloxone for opiate binding sites with IC50 values of approximately 1 microM. This effect can be blocked by excess naloxone but not by the noradrenaline uptake inhibitors cocaine or desipramine. Other drugs containing the 2-chloroalkylamine structure--phenoxybenzamine, dibenamine, chloroethyl clonidine, the cholinotoxin AF-64 and 2-dimethylaminoethyl chloride--were similarly tested. Phenoxybenzamine and dibenamine were also able to compete with [3H]-naloxone for binding at the opiate receptor. Experiments in vivo demonstrated that DSP4, like other opiates, can rapidly reduce LH secretion in the rat. This effect is prevented by naloxone but not by desipramine. These data suggest the use of caution in interpreting the results of experiments in which DSP4 and xylamine are used as "specific" noradrenergic uptake inhibitors or as neurotoxins.

Amines↗
PubMed1985

Naproxen sodium in the treatment of migraine.

Seventy patients with classical or common migraine were treated during their attacks with either naproxen sodium or placebo in a randomised, double-blind parallel group study. The initial dose of naproxen sodium was 825 mg followed one hour later by a further 550 mg, if symptoms were the same or had improved. If the migraine symptoms had worsened, patients were offered an escape analgesic combination of 1000 mg paracetamol and 10 mg metoclopramide. Patients were assessed at monthly intervals for changes in the severity and duration of headache, premonitory symptoms (mainly visual disturbances) and photophobia, nausea and vomiting associated with migraine attacks that had occurred since the previous visit. Patients were studied for a maximum of ten attacks and significant improvement was observed in the severity and duration of headache when the patients were on naproxen sodium. Also the premonitory symptoms and photophobia improved significantly on naproxen sodium and significantly less rescue analgesics were required. Patients suffering from common migraine had less severe headaches and photophobia when taking naproxen sodium than when taking placebo and the headaches were shorter in duration and patients took less rescue analgesic. No significant difference was observed between the treatment groups in patients with classical migraine. Ten patients in the placebo group and six in the naproxen sodium group reported side-effects but these were possibly related to the use of rescue medication. Naproxen sodium proved safe and effective in common migraine attacks, but in this study efficacy was not established for classical migraine.

Adolescent↗
PubMed1985

Migraine art.

An analysis is made of 207 drawings and paintings entered for a migraine art competition. All types of visual disturbances were depicted. One hundred and fifty-four of the paintings showed spectral appearances with fortification or teichopsia in 99. Sixty-two showed either a partial or complete hemianopic loss. Metamorphopsia was seen in 32 and pain was depicted in some form or another in 80. Situational or trigger factors were shown in 23.

Art↗
PubMed1985

Gonadal steroid-induced modification of opiate binding sites in anterior hypothalamus of female rats.

It has been previously shown that treatment with estradiol valerate (EV) or 17 beta-estradiol produces enhanced tritiated naloxone binding in the hypothalamus of the rat. In the present study, the following questions were addressed: Does this effect occur in the preoptic and anterior hypothalamic areas (regions associated with the cyclic gonadotropin surge)? Is chronic estradiol (E2) exposure essential in producing a long-term elevation in opiate binding? Is the effect steroid specific? The results indicated that chronic, but not acute, exposure to estradiol induces and maintains enhanced binding in the anterior hypothalamus. E2 exposure was most effective in this regard, testosterone (T) significantly less so, and 5 alpha-dihydrotestosterone (DHT) caused no elevation in binding above castrate control levels. Furthermore, both T and DHT significantly inhibited the estradiol effect. In addition, intact animals showed significantly less binding than their ovariectomized counterparts, suggesting that the ovary normally produces a factor that suppresses opiate binding. Enhancement of anterior hypothalamic opiate binding is therefore dependent on chronic exposure to E2, and the marginal effects of T are probably due to in situ aromatization. E2 enhancement of opiate binding may be causal in producing the hypothalamic aberration that results in the EV-induced polycystic ovarian condition.

Animals↗
PubMed1985

Migraine--treatment of acute attack.

The treatment of an acute attack of classical or common migraine is sleep, an antinauseant such as metoclopramide, an analgesic, either aspirin or paracetamol, and in some patients 1 or 2 mg of ergotamine tartrate. Treatment should be given as early in the attack as possible and all drugs should, if possible, be given in a soluble or effervescent form. When vomiting occurs early in the attack, treatment is best given by suppository, inhalation or intramuscular injection. Ergotamine tartrate is only necessary in about one third of attacks and when used is best given by suppository or inhalation. Doses of ergotamine tartrate higher than 2 mg per attack or 6 mgs per week may cause toxic symptoms as may the abuse of analgesics.

Acetaminophen↗
PubMed1985

Infantile ovariectomy potentiates the stimulatory effect of oestrogen/progesterone on LH secretion in the rat.

Ovariectomy of prepubertal rats (9 days of age) eliminates the ability of the opiate peptide FK 33-824 to inhibit LH secretion when tested 19 days later. We have investigated whether this removal of opiate inhibition would modify the LH/FSH response to stimulation with oestradiol benzoate/progesterone priming. Ovariectomy of rats during infancy (9 days after birth) amplifies the stimulatory effects of these steroids on LH/FSH secretion when tested 19 days later. This amplification was not seen in rats ovariectomized before (day 24) or after puberty (day 43) and tested 19 days later. The pituitary content of LH/FSH does not appear to contribute to this phenomenon, though increased responsiveness to injected gonadotrophin-releasing hormone (GnRH) is clearly involved; ovariectomy at day 9 is considerably more effective than ovariectomy at day 24 of life in enhancing the response to GnRH. We conclude that infantile ovariectomy either removes, or prevents the development of, a hypothalamic inhibitory mechanism which normally modulates the responsiveness of the pituitary to stimulation with GnRH.

Animals↗
PubMed1985

Is parathyroidectomy of benefit in primary hyperparathyroidism?

A retrospective survey was performed on 265 patients with primary hyperparathyroidism who had received three forms of treatment on a non-randomised basis. 'Successful' surgery (normalisation of serum calcium) was carried out in 142 patients, 'unsuccessful' surgery (persistence of hypercalcaemia after neck exploration) in 33 and no surgery in 90. Patients subjected to surgery were significantly younger than patients in the unoperated group and their serum calcium values at the time of decision were approximately 10 per cent higher. The mean follow-up period was significantly longer in the operated groups. The percentages of patients who had died were similar in each group. Clinical events relating to renal stones depended on the presence or absence of calculi at the time of decision rather than on the method of treatment. At the time of follow-up the prevalence of hypertension, renal impairment and vertebral crush fractures were similar in all three groups. Forearm osteo-densitometry showed a higher bone mineral content in the 'successful' group than in the other two groups. In spite of the selection bias inherent in a study of this kind, it is clear that untreated hyperparathyroidism is compatible with long survival and a lack of demonstrable deleterious effects on kidney and bone.

Bone Diseases↗
PubMed1984

Clinical disorders in patients with hyperprolactinaemia. Experience with 59 patients.

Fifty-nine patients with hyperprolactinaemia and presumed, or histologically proven, pituitary tumours were identified within a seven-year period. The wide variety of clinical presentation, the natural history, and the problems associated with therapy are highlighted in several selected case presentations which include both patients with invasive tumours and those with no radiological abnormalities and minimal symptoms. The special considerations involved in a planned pregnancy in a patient with hyperprolactinaemia are emphasized.

Acromegaly↗
PubMed1984

The E receptor regulates interferon-gamma production: four-receptor model for human lymphocyte activation.

The E receptor (binds sheep erythrocytes) is found on virtually all human T cells. Here we show that a monoclonal antibody 9.6, which recognizes and binds the E receptor, inhibited interferon-gamma production by human peripheral blood mononuclear leukocytes induced with the mitogens phytohemagglutinin, concanavalin A, Staphylococcal enterotoxin A and the monoclonal antibody OKT3. Metabolic activation (RNA and DNA synthesis) in human peripheral blood mononuclear leukocytes in response to mitogens was also sharply inhibited by 9.6. This inhibitory effect occurred early during the induction phase since 9.6 had much diminished inhibitory effects when added 15-24 h after induction; peak IFN-gamma production and DNA synthesis occurred 3-4 days post induction. An early event inhibited by 9.6 appeared to be interleukin 2 (IL 2) receptor formation since: (a) the ability of mitogen-stimulated peripheral blood mononuclear leukocytes to absorb IL 2 was inhibited by 9.6, and (b) lines of T lymphocytes which already expressed IL 2 receptors were largely resistant to the inhibitory effects of 9.6 on IFN-gamma production and DNA synthesis. The tumor promoters 12-O-tetradecanoyl phorbol-13-acetate and teleocidin largely reversed the inhibition by 9.6 of IFN-gamma production and metabolic activation induced by mitogens. A model for the control of IFN-gamma induction involving four receptors, those for mitogens, tumor promoter, IL 2 and erythrocyte, is proposed.

Antibodies, Monoclonal↗
PubMed1984

Differential effects of flurothyl- and electro-convulsive shock on sexual maturation and prolactin release in the rat.

The effects of single and repeated seizures on luteinizing hormone (LH), follicle stimulating hormone (FSH) and prolactin secretion and on the onset of sexual maturation in rats are described. In addition, the influence of convulsions generated electrically (electroconvulsive shock, ECS) and chemically (using flurothyl) are compared. Repeated flurothyl convulsions and ECS (one daily convulsion from age 24 days) significantly delay vaginal opening in female rats. The incidence of first ovulation at maturation is reduced to 20% compared with 70-100% for untreated groups. Body and adrenal weights in immature rats are not modified by flurothyl convulsions. Repeated ECS does not influence adrenal weight although somatic growth is inhibited. In an effort to clarify the mechanism of action of convulsions on puberty onset, we examined acute changes in LH, FSH and prolactin secretion and the surge response of LH/FSH to gonadal steroid priming. A single flurothyl convulsion potently inhibits prolactin secretion. In contrast, an ECS acutely stimulates prolactin release in male and female rats. Convulsive seizures do not consistently alter tonic gonadotropin output. However, both flurothyl convulsions and ECS attenuate estradiol benzoate/progesterone-induced LH and FSH surges in ovariectomized rats though this is apparently not mediated by dopamine/prolactin since bromocriptine treatment delays sexual maturation without preventing ovulation at first estrus. Similarly, bromocriptine does not disrupt LH/FSH surges induced by gonadal steroid treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Difficulty in diagnosing hemobilia from a hepatic artery aneurysm: value of endoscopic retrograde cholangiography.

A case of hemobilia due to a hepatic artery aneurysm is described. Despite 2 arteriograms and 2 laparotomies, the cause of the bleeding remained undetected until a further selective cannulation of the celiac axis artery was performed. Endoscopic retrograde cholangiography demonstrated that postoperative jaundice was not due to obstruction and outlined the aneurysm within a hepatic duct.

Adult↗