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Biomedical subjects

P Dean

Publications and source records attributed to P Dean.

At least 145 records · Page 8Linked to original sources

Human papillomavirus structural antigens in squamous papillomas of the male urethra.

Twenty-five squamous papillomas of the male urethra were examined for the presence of human papillomavirus (HPV) whole (structural) virion antigens by a peroxidase-antiperoxidase technique having immunospecificity against genus-specific (common) antigens of the papillomavirus genus. Eleven of 25 (44 per cent) lesions were positive for HPV. The positive reaction was invariably intranuclear in the superficial epithelium. Evidence suggests that these papillomas arise by HPV infection of metaplastic squamous epithelium and not transitional epithelium. This study shows that at least some squamous papillomas of the male urethra are associated with HPV infections and suggest that this lesion may play an important role in venereally transmitted diseases such as cervical dysplasia and condylomas of the vulva and anus.

Adolescent↗

[Urologic complications in kidney transplants: experience in 274 transplants].

The urological complications after a renal transplantation still represent an event anything but rare, ranging, according to the different statistics, from 0.9% up to 23%, with a mortality between 0 and 25%. In this work done by the Verona Centre the experience on 274 transplantations is reported. The urological complications weighed with 6.2% and absence of mortality among the patients. The importance of the prevention and precocious diagnosis is confirmed.

Adolescent↗

Suppression of apomorphine-induced oral stereotypy in rats by microinjection of muscimol into midbrain.

Rats with large lesions of the superior colliculus do not display the oral stereotypy normally induced by high systemic doses of dopamine-agonists. It has been suggested that collicular lesions have such an effect because they destroy the GABAergic nigrotectal pathway. This suggestion was investigated by observing the effects of bilateral microinjections of the GABA-agonist muscimol into midbrain sites in rats given 8 mg/kg subcutaneous apomorphine. A low dose of muscimol (25 ng in 0.5 ul saline/side) injected into regions of the superior colliculus with nigrotectal innervation almost abolished apomorphine-induced licking and gnawing. Control microinjections of saline into the superior colliculus, or of muscimol into overlying cerebral cortex, were ineffective. This result is consistent with the GABAergic nigrotectal projection being important for the expression of dopamine-related oral stereotypy. It was also found, however, that 25 ng of muscimol suppressed oral stereotypy when microinjected into the mesencephalic reticular formation underlying the superior colliculus. The anatomical basis of this latter effect is uncertain.

Animals↗

Screening for breast cancer in a high-risk series.

A unique cohort of women at increased risk of breast cancer because of prior X-ray treatment of acute mastitis and their selected high-risk siblings were offered periodic breast cancer screening including physical examination of the breasts, mammography, and thermography. Twelve breast cancers were detected when fewer than four would have been expected based on age-specific breast cancer detection rates from the National Cancer Institute/American Cancer Society Breast Cancer Demonstration Detection Projects. Mammography was positive in all cases but physical examination was positive in only three cases. Thermography was an unreliable indicator of disease. Given the concern over radiation-induced risk, use of low-dose technique and of criteria for participation that select women at high risk of breast cancer will maximize the benefit/risk ratio for mammography screening.

Adult↗

Increased food intake following the manipulation of intracerebral dopamine levels with gamma-hydroxybutyrate.

The administration of gamma-hydroxybutyric acid (GHB) initially causes a temporary "sleep-like" state during which there is an increase in forebrain dopamine levels. The present series of experiments examined whether in the period following the GHB-induced behavioural depression, when accumulated dopamine is dispersed, there is any behavioural evidence of increased dopaminergic activity. The first experiment, in which GHB was injected directly into the cerebral ventricles, demonstrated that in the immediate post-recovery period rats exhibited various forms of stereotyped oral behaviour and stereotyped sniffing. Unexpectedly, it was also observed that if food were present animals preferred to eat. The nature of this feeding response was examined in two further experiments. Firstly, it was shown that in the period following the behavioural depression animals would perform, in a dose-dependent fashion, an operant response which was rewarded by food. Secondly, the GHB-induced increase in feeding was abolished by the pre-treatment of animals with either the dopamine synthesis inhibitor alpha-methyl-p-tyrosine, or the dopamine receptor blocker haloperidol. These data indicate that (i) in the period when it is known that the GHB-induced accumulation of dopamine is dispersing, there is behavioural evidence of increased dopaminergic activity; (ii) the feeding response is not a simple oral reflex; and (iii) in addition to being essential for food intake dopaminergic transmission may play a direct role in the production of feeding.

Amphetamine↗

Oral behaviour induced by intranigral muscimol is unaffected by haloperidol but abolished by large lesions of superior colliculus.

It has been suggested that the GAbAergic striatonigral projection may form part of the efferent pathway responsible for the expression of dopamine-related oral behaviour. Consistent with this suggestion are reports that bilateral injection of the GABA agonist muscimol can produce stereotyped gnawing and biting. We report here two experiments on this effect: (1) A dose of the dopamine receptor blocker haloperidol (0.4 mg/kg), which effectively antagonised oral stereotypy induced by systemically administered apomorphine or intranigral carbachol, had no effect on either the latency or the intensity of the gnawing produced by intranigral muscimol (1 nM); (2) large lesions involving the superior colliculus which effectively suppressed the oral stereotypy induced by 8 mg/kg apomorphine completely abolished the gnawing induced by intranigral injection of muscimol. Collicular lesions suppressed both the gnawing which occurred spontaneously and that elicited by a perioral probe. These findings are consistent with the view that the substantia nigra is a relay station between the caudate nucleus and the superior colliculus in an efferent pathway mediating dopamine-related oral behaviour. In addition, they raise the possibility that such behaviour is produced by the sensitisation of a collicular-mediated perioral reflex.

Animals↗

A quantitative analysis of stereotyped gnawing induced by apomorphine.

An apparatus was designed and constructed to enable a quantitative analysis of the stereotyped gnawing produced by the dopamine agonist apomorphine. Using this apparatus it was discovered that increasing the subcutaneous dose of apomorphine increased (1) the number of animals that gnawed, and (2) the duration of gnawing in those animals that gnawed at all doses. Other aspects of apomorphine-induced gnawing, in particular the latency to respond and the frequency and duration of individual gnaws, were relatively unaffected. Likely properties of the system responsible for the organization of sterotyped gnawing are discussed.

Animals↗

Locomotor activity of rats in open field after microinjection of procaine into superior colliculus or underlying reticular formation.

Whereas large lesions of the superior colliculus in rats increase locomotor activity in the open field, bilateral collicular microinjections of muscimol (an agonist of the inhibitory neurotransmitter GABA) have been reported to reduce open-field activity. This difference might be due to muscimol's acting on a subpopulation of collicular neurones, or to some feature of the microinjection technique. The issue was investigated by observing open-field behavior after reversible lesions produced by bilateral microinjections of the local anaesthetic procaine (10-300 micrograms in 0.5 microliter) into midbrain sites. Injections of procaine into the superior colliculus produced effects similar to those reported after muscimol injections: both locomotor activity and other exploratory responses were suppressed, with the rats spending much of their time motionless in an alert posture. In contrast, animals with injections of procaine into the mesencephalic reticular formation (MRF) ventral to the superior colliculus resembled rats given large collicular lesions: they showed very striking increases in locomotor activity, while their rearing and exploratory head movements were reduced. It is suggested that in some experiments large collicular lesions may have increased locomotor activity in the open field because they invaded underlying MRF. However, it is also possible that in rodents the acute effects of collicular inactivation, as assessed by microinjection of muscimol or procaine, are different from the chronic effects that are observed in experiments with electrolytic or radiofrequency lesions.

Animals↗

Rewarding effects of hypothalamic self-stimulation altered by unilateral lesions of superior colliculus in rats.

The effects of unilateral lesions of the superior colliculus were determined on self-stimulation of the medial forebrain bundle. It was found that the lesions had different effects depending upon the precise location of the stimulating electrode: self-stimulation on far-laterally located electrodes was abolished while on more medially placed electrodes this behaviour was enhanced. These data are inconsistent with explanations of intracranial self-stimulation which treat it as a unitary phenomenon.

Animals↗

A flow system for partial automation of plating efficiency tests.

A flow system that sterilely deposits a known number of cells into a collection vessel has been constructed and evaluated. In this device, the cells from a single-cell suspension flow through a nozzle that constrains them to the center of the emerging jet. The cells in the jet are illuminated by a 0.5-mW helium-neon laser; they are detected, sized and counted on the basis of the light scattered as they pass through the laser beam. The device has been used for plating efficiency tests in a tissue culture laboratory. We found that it saved considerable labor by eliminating the dilution step from the standard plating efficiency procedure. The biologic effect of machine plating was determined by comparing plating efficiencies of KHT, CHO-T5, and CHO-AA8 cells established by hand plating with those established by machine plating. Results indicate that machine plating reduces the plating efficiency of the CHO-T5 cells while the plating efficiencies of the CHO-AA8 and KHT cells are unaffected.

Animals↗

Grating detection and visual acuity after lesions of striate cortex in hooded rats.

The ability of rats to detect high-contrast square-wave gratings over a range of spatial frequencies was measured before and after ablation of striate cortex. The animals relearnt to detect low-frequency gratings very quickly after operation, and their acuity was reduced from 1.0 c/deg to about 0.7 c/deg. These effects were in striking contrast to those produced by larger posterior cortical ablations, which included both striate and prestriate cortex (Dean 1978); after the larger lesions, rats required many weeks of retraining to detect even low-frequency gratings and their acuity was reduced to 0.3 c/deg. The difference in the effects of the two lesions suggested that the rats with striate ablation were using information about spatial contrast that was relayed either by spared remnants of the geniculo-cortical pathway, or by the pathway from superior colliculus to prestriate cortex via the lateral posterior nucleus. To try and distinguish between these possibilities, the destriate rats were given a further lesion of the superior colliculus. This second lesion severely disrupted contrast detection: the animals made about as many errors as rats with large posterior cortical removal in relearning to detect a low-frequency grating, which is about 20 to 30 times as many as after either striate cortex or superior colliculus lesions alone. This result suggests that rats, like other mammals, can use spatial information conveyed in the tectocortical path when striate cortex has been destroyed.

Animals↗

Gnawing and changes in reactivity produced by microinjections of picrotoxin into the superior colliculus of rats.

Lesions of the superior colliculus in rats attenute the oral stereotypy produced by systemic administration of dopamine agonists. Current evidence suggest that such drugs affect the superior colliculus by reducing transmission in the inhibitory GABAergic nigrotectal pathway. To investigate whether the superior colliculus plays a direct role in producing stereotyped oral movements, the present experiment therefore examined the effects of collicular microinjections of the GABA antagonist picrotoxin on the behaviour of rats observed in an open-field. Gnawing was observed after injections of picrotoxin (25 ng) into sites in the intermediate and deep layers of the superior colliculus, consistent with the superior colliculus playing a direct part in producing the stereotyped gnawing seen after systemic administration of dopamine agonists. However, gnawing was only observed after a period in which the animal showed strong avoidance reactions to stimuli that normally evoked orienting or little reaction. This change in reactivity was observed after injections of picrotoxin into all parts of the colliculus, but the most sensitive (responding to doses as low as 12.5 ng) were mainly in the superficial and intermediate layers. It appears that there may be more than one GABAergic system within the superior colliculus.

Animals↗

Collicular picrotoxin alleviates akinesia but not sensory neglect in rats with bilateral 6-hydroxydopamine lesions of ventral midbrain.

Anatomical and biochemical investigations have suggested that GABA transmission in the superior colliculus consequent upon activity of the nigrotectal pathway is increased following 6-hydroxydopamine (6-OHDA) lesions of the ascending dopamine systems. Moreover, it has been proposed that this increase in inhibitory activity within the colliculus may be responsible for the sensory neglect commonly observed after dopamine denervation. The present experiment sought to test this proposal by examining the effects of injections of the GABA antagonist picrotoxin into the superior colliculus of 6-OHDA lesioned rats, in the hope that the neglect caused by the 6-OHDA would be reversed. However, in 33 of 36 cases studied intracollicular microinjections of picrotoxin produced no detectable improvement in orientation to sensory stimuli, although a wide range of other behavioural effects was observed. These included stereotyped exploratory movements (e.g. head waving, walking, sniffing and rearing) similar to those produced in the 6-OHDA treated rats by systemic injection of apomorphine (0.1 mg/kg). These data indicate that 6-OHDA lesions of substantia nigra and ventral midbrain areas do not produce sensory neglect simply by increasing GABA transmission within the nigrotectal pathway. Instead, such an increase in nigrotectal activity may impair production of particular kinds of movement, possibly related to exploratory behaviour.

Animals↗

Visual pathways and acuity hooded rats.

Three experiments on the effects of lesions of the visual system on contrast-detection in hooded rats are described, in which the ability of rats to detect stationary high-contrast square-wave gratings of various fundamental frequencies presented in the central visual field was measured before and after operation. The results suggested the following conclusions: (i) The pathways from retina to striate cortex via dorsal lateral geniculate nucleus (dLGN) conveys information about high spatial frequencies sufficient for normal detection of these gratings, that is up to about 1 cycles/deg. It may be the only pathway to carry this information, and may thus play a unique role in the analysis of fine detail. The high-frequency information is probably relayed from striate cortex to extrastriate cortex, rather than to subcortical sites. (ii) The superior colliculus receives information from the retina up to at least 0.7 cycles/deg, which it then relays to extrastriate visual cortex, probably via the lateral posterior nucleus of the thalamus. (iii) Neither the projections from superior colliculus to other, non-thalamic sites nor the remaining pathways from the retina (e.g. to ventral LGN) appear to carry contrast information higher than 0.3 cycles/deg. These sets of projections therefore do not appear to be used for precise analysis of stationary scenes. These findings suggest that there are considerable similarities between the visual systems of rats and other mammals with respect to the routing of information about stationary spatial contrast, and may help to explain the results of some experiments that have used tasks besides contrast-detection to assess the visual capacities of rats after lesions.

Animals↗