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Biomedical subjects

M Watson

Publications and source records attributed to M Watson.

At least 217 records · Page 12Linked to original sources
PubMed1985

Towards a psychobiological model of cancer: psychological considerations.

To date, the evidence relating to the role of stress and psychological variables in cancer aetiology and promotion is contradictory. We have attempted to clarify the issues by presenting an hypothetical psychobiological model. Two components of this model are described: (1) a characteristic behaviour pattern (Type C) which may mediate stress reactions and (2) the biological concomitants of this behaviour pattern. The mechanisms of cancer initiation and promotion are described in a companion paper (Pettingale). The main hypothesis advanced by this model is that the psychological factors described may promote cancer development; the model is offered for investigation.

Emotions↗
PubMed1985

Functional and biochemical basis for multiple muscarinic acetylcholine receptors.

The novel antimuscarinic compound pirenzepine (PZ) has generated considerable interest in the basis and the implications of muscarinic acetylcholine receptor (mAChR) heterogeneity. [3H]PZ has been used extensively to identify and characterize the putative M1 (high affinity for PZ) mAChR subtype, which predominates in central nervous system (CNS) and ganglia. The heterogeneity sensed by PZ is not identical to the heterogeneity sensed by agonists. Differences in effector coupling do not necessarily provide a simple explanation for the molecular basis of these putative M1 and M2 subtypes. Therapeutic and untoward effects of muscarinic drugs may be mediated by independent mAChR subpopulations which may be pharmacologically exploited to produce more highly selective as well as efficacious new drugs.

Alzheimer Disease↗
PubMed1985

Major ruptures of the rotator cuff. The results of surgical repair in 89 patients.

Major ruptures of the rotator cuff were repaired in 89 patients over a six-year period, using an approach through the split deltoid muscle and the bed of the excised outer centimetre of the clavicle. Review of these patients showed that poor results were associated with larger cuff defects, with more pre-operative steroid injections and with pre-operative weakness of the deltoid muscle. A randomised prospective study showed that repair followed by splinting in abduction gave no better results than repair followed by resting the arm at the side. Excision of the coraco-acromial ligament was associated with worse results than leaving its divided halves in situ. Follow-up showed that the results continued to improve for two years after operation; their quality was maintained in patients less than 60 years old, but in those over 60 there was deterioration with time.

Adult↗
PubMed1985

Regional differences in ethylcholine mustard aziridinium ion (AF64A)-induced deficits in presynaptic cholinergic markers for the rat central nervous system.

Several highly selective biochemical markers were used to assess the persistent central cholinergic dysfunction which accompanies administration of the cholinergic neurotoxin ethylcholine mustard aziridinium ion (AF64A). Rats received a single bilateral intracerebroventricular injection of AF64A (3 nmol/3 microliter/side) or vehicle and measurements were carried out in the cerebral cortices, hippocampi and corpora striata at 7 and 21 days postinjection. The drug binding sites of muscarinic cholinergic receptors, as revealed by high-affinity binding of (-)-[3H]quinuclidinyl benzilate (a classical muscarinic antagonist), [3H]pirenzepine (a selective antagonist of the putative M1 muscarinic receptor subclass) and (+)-[3H]cis-methyldioxolane (a potent muscarinic agonist), were not significantly affected by AF64A treatment. As reported previously, activity of the cholinergic synthetic enzyme choline acetyltransferase was reduced markedly (60-65%) in the hippocampi of AF64A-treated rats. A similar reduction was noted in high-affinity binding of [3H]hemicholinium-3 (a putative radioligand for sodium-dependent high-affinity choline uptake sites on cholinergic nerve terminals) in hippocampal membranes (59-65%). However, in the cerebral cortex, these presynaptic cholinergic markers were differentially altered by AF64A pretreatment (choline acetyltransferase, unchanged; [3H]hemicholinium-3 binding, reduced by 59-65%). These results indicate that a single intracerebroventricular injection of AF64A promotes biochemical and possibly functional deficits in presynaptic cholinergic nerve terminals distal from the injection site while having minimal influences upon muscarinic cholinergic receptor populations.

Animals↗
PubMed1985

Differential ontogeny of putative M1 and M2 muscarinic receptor binding sites in the murine cerebral cortex and heart.

Studies with [3H]pirenzepine [( 3H]PZ) suggest that this nonclassical muscarinic antagonist selectively identifies putative M1 muscarinic receptors. We now compare the ontogeny of these putative M1 sites, identified by high-affinity [3H]PZ binding, with sites identified by the classical antagonist (-)-[3H]quinuclidinyl benzilate ((-)-[3H]QNB) in murine cerebral cortical and cardiac homogenates. Dissociation constants (Kd) for [3H]PZ (2.1-6 nM in the cortex and 2.0-21 nM in the heart) and for (-)-[3H]QNB (10-28 pM in the cortex and 10-39 pM in the heart) are similar in adult and neonatal tissues, whereas receptor density (maximum binding, femtomoles per milligram of protein) varies significantly. Cerebral cortical [3H]PZ binding rises from 14% at birth, to 88% of adult levels by day 14, peaks at 128% at day 28 and falls to the mean adult level of 606 fmol/mg of protein. Cerebral cortical (-)-[3H]QNB binding parallels [3H]PZ binding. Conversely, parallel studies show cardiac (-)-[3H]QNB density is 3- to 17-fold greater than the comparable density of high-affinity [3H]PZ binding sites throughout ontogeny. We conclude that: 1) the high ratio of [3H]PZ binding to (-)-[3H]QNB binding identifies the murine cerebral cortex as a tissue which contains predominantly putative M1 muscarinic binding sites; 2) the relatively low ratio of [3H]PZ binding to (-)-[3H]QNB binding throughout ontogeny identifies the murine heart as a tissue which contains primarily the putative M2 muscarinic binding site; and 3) M1 and M2 receptor binding sites show distinct developmental curves in the cerebral cortex and heart.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Light microscopic autoradiographic localization of [3H]pirenzepine and [3H](-)quinuclidinyl benzilate binding in human stellate ganglia.

We have utilized the LKB Ultrofilm method of autoradiography to anatomically localize putative M1 and M2 muscarinic receptor subtypes in human stellate ganglia. Ten micron sections were labeled in vitro with either 1 nM of the classical antagonist [3H](-)quinuclidinyl benzilate ([3H](-)QNB) or 20 nM of the non-classical antagonist [3H]pirenzepine ([3H]PZ), using 1 microM atropine sulfate to define non-specific binding for both ligands. Our results indicate that [3H](-)QNB and [3H]PZ binding sites are distributed within the principal ganglion cells and nerve bundles.

Autoradiography↗
PubMed1984

Effect of dopamine agonist withdrawal after long-term therapy in prolactinomas. Studies with high-definition computerised tomography.

The clinical, radiological, and biochemical effects of dopamine agonist withdrawal after long-term treatment were investigated in seven women and eight men who had been treated for prolactinomas for 1.5 to 7 (mean 3.7) years. Before treatment, serum prolactin concentrations were 1473 to 115 000 mU/l, all patients had abnormal radiological findings, and six had suprasellar extensions of pituitary tumours. Treatment with either bromocriptine or pergolide relieved symptoms and suppressed prolactin secretion in most patients. The size of the residual tumour was defined by doing fourth generation computerised tomographic scans immediately before termination of therapy, and evidence of tumour re-expansion was sought on scans repeated 5-39 weeks later. After discontinuation of treatment, symptoms recurred in 13 of 15 patients and hyper-prolactinaemia redeveloped in 14. Other pituitary function tests remained unchanged or improved. In 13 of 15 patients tumour or gland size did not change after withdrawal of treatment. One man had a marginal increase in tumour size, while in another the pituitary tumour shrank. Thus, although cessation of long-term dopamine agonist therapy leads to recurrence of symptoms and hyperprolactinaemia, rapid tumour regrowth is uncommon and of small extent, and other pituitary function is not altered in the short term.

Adult↗
PubMed1984

Reaction to a diagnosis of breast cancer. Relationship between denial, delay and rates of psychological morbidity.

Psychological responses were measured in a newly diagnosed group of breast cancer patients during their hospital stay for primary surgical treatment by mastectomy. The aim was to assess the extent to which patients responded to the stress of a cancer diagnosis by denying the seriousness of the illness, and how this related to both level of distress and prior delay in seeking treatment. The data indicated that patients who denied the seriousness of a cancer diagnosis experienced significantly less mood disturbance during this period than those who were more accepting of the implications of this diagnosis. These findings suggest that a denial rather than a confrontation-coping-response may effectively reduce the short-term distress experienced during this initial period of hospitalization. Contrary to predictions, we failed to show an association between the length of delay in seeking treatment and denial of the diagnosis.

Anxiety↗
PubMed1984

Cerebellar norepinephrine depletion and impaired acquisition of specific locomotor tasks in rats.

Previous work in our laboratory has shown that norepinephrine (NE)-depleted rats manifested impaired acquisition of a locomotor task as measured in a new rod runway paradigm. This paradigm involved the initial training of water-deprived rats on an equally spaced regular rod arrangement (REG), and subsequent testing, after intracisternal 6-hydroxydopamine (6-OHDA; 3 X 25 micrograms/microliter free base) infusion, on a more difficult irregular rod arrangement (IRR). These NE-depleted animals manifested impaired acquisition of the task as measured by running times (RT, 25 trials/day) over a 4 day post-infusion test period (IRR). In this present study, this same REG/IRR paradigm was employed in combination with a localized 6-OHDA lesion of the coeruleo-cerebellar pathway. A bilateral infusion of 6-OHDA (8 micrograms/2 microliters) induced cerebellar noradrenergic deafferentation (26% of controls) and produced a significant impairment of 4 day post-infusion RT. Thus, the coeruleo-cerebellar-lesioned rats demonstrated acquisitional impairment when tested on the new locomotor task (IRR). Moreover, the degree of impaired acquisitional, but not initial post-infusion motor performance, was found to correlate directly with the degree of cerebellar noradrenergic deafferentation. Furthermore, these rats showed no arousal, motivational or general cognitive learning deficits since no significant differences were observed in runway intertrial interval times, open field behavior, or in reversal of a T-maze position habit. Thus, cerebellar NE appears to be strongly associated with the adaptive ability to coordinate and choreograph the movements necessary to perform in this locomotor task.

Animals↗
PubMed1984

High-affinity [3H]pirenzepine binding to putative M1 muscarinic sites in the neuroblastoma x glioma hybrid cell line (NG 108-15).

The specific binding of both the non-classical antagonist [3H] pirenzepine ( [3H]PZ) and the classical antagonist [3H](-)quinuclidinyl benzilate ( [3H](-)QNB) was determined in parallel assays of the mouse neuroblastoma x rat glioma hybrid cell line (NG 108-15). Saturation isotherms yielded a Kd = 4.0 nM and Bmax = 27.8 fmoles/mg protein for [3H]PZ and a Kd = 17.2 pM and Bmax = 53.2 fmoles/mg protein for [3H](-)QNB. The inhibition data of pirenzepine vs [3H](-)QNB was best fit to a 2-site binding model revealing both a high affinity pirenzepine site (72%, KH = 10.3 nM) and a low affinity site (28%, KL = 97.5 nM). [3H]PZ competition studies demonstrated stereospecificity, steep inhibition curves for muscarinic antagonists (Hill coefficients close to 1), and a shallow inhibition curve for a muscarinic agonist. These results indicate that muscarinic receptors on NG 108-15 cells may be subclassified (M1/M2) on the basis of the discriminative capability of [3H]PZ.

Animals↗
PubMed1984

[3H]Pirenzepine identifies putative M1 muscarinic receptors in human stellate ganglia.

The specific binding of [3H]pirenzepine ( [3H]PZ) and [3H](-) quinuclidinyl benzilate ( [3H](-)QNB) was investigated in homogenates of human stellate ganglia. [3H]PZ saturation isotherms yielded a Kd of 14 nM and Bmax of 16.7 fmol/mg protein, while [3H](-)QNB binding curves yielded a Kd of 59 pM and Bmax of 33.0 fmol/mg protein. This represents the greatest proportion of high affinity [3H]PZ labeling, relative to [3H](-)QNB, seen in any peripheral tissue examined thus far.

Adult↗
PubMed1984

Restudy of the original marker X family.

Restudy of the original marker-X family confirmed recent observations that this XLMR disorder is associated with large testes and slightly abnormal ears. However, other aspects of the phenotype were variable and a distinct facies was not evident. Significant differences in marker-X frequency between two laboratories processing the same samples were observed. Possibly, the combination of more cells and a longer culture time in one laboratory led to a greater depletion of critical nutrients and a higher frequency of the marker-X, but additional studies are needed. No evidence was found of a diminishing frequency of the marker-X over a 15 year period.

Abnormalities, Multiple↗