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Biomedical subjects

P Dean

Publications and source records attributed to P Dean.

At least 127 records · Page 7Linked to original sources

Altered cell cycle distributions of cultured human lymphoblasts during cytotoxicity related to adenosine deaminase inhibition.

Serial-flow cytometric analysis of DNA content of T lymphoblasts (MOLT-4) and B lymphoblasts (MGL-8) was performed to correlate the cytotoxic properties of adenosine deaminase inhibition with alterations of DNA synthesis and disruptions of the cell cycle. The addition of deoxyadenosine up to 50 mumol/L potently decreased the growth of T lymphoblasts, and these changes were enhanced with the addition of 100 mumol/L homocysteine thiolactone. These conditions caused a virtual absence of cells from S and G2M phases after 24 hours. The DNA distribution was similar in cells cultured for 24 hours in 50 mumol/L deoxyguanosine or 2.5 mumol/L hydroxyurea. These observations suggested accumulation of cells in the G1 phase. T lymphoblasts cultured with up to 50 mumol/L adenosine had a substantial decrease in growth, which was not modified by the addition of homocysteine thiolactone. Cell cycle distributions of T lymphoblasts cultured for 24 to 48 hours under these conditions showed mild decreases in the G2M population. The addition of adenosine up to 50 mumol/L decreased the growth of B lymphoblasts, and these changes were enhanced by the addition of 100 mumol/L homocysteine thiolactone. These conditions induced mild decreases in the S-phase population in B lymphoblasts. The addition of deoxyadenosine, even with homocysteine thiolactone, did not modify growth in B lymphoblasts and the cell-cycle distributions were indistinguishable from distributions of control populations after 24 and 48 hours. The observations provide independent support for a reduction of DNA synthesis associated with cytotoxicity during adenosine-deaminase inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Deaminase Inhibitors↗

Dissociation of stimulation-bound feeding and apomorphine-induced gnawing by lesions of superior colliculus.

The intense stereotyped gnawing induced by high doses of apomorphine is almost abolished by large bilateral lesions of the superior colliculus. It has been argued that the feeding produced by electrical stimulation of the lateral hypothalamic area is closely related to dopamine-mediated oral stereotypies; if so, it might be expected that lesions of the superior colliculus would also disrupt stimulation-bound feeding. Feeding was obtained from 14 hypothalamic electrodes in 8 hooded Lister rats. Subsequent electrolytic lesions of the superior colliculus had no overall effect on this behaviour from 13 of the 14 electrodes, even though the lesions reduced the gnawing induced by 8-20 mg/kg apomorphine to less than 10% of its preoperative intensity. It is concluded that stimulation-bound feeding and apomorphine-induced gnawing are not dependent on identical neural circuitry, and therefore stimulation-bound feeding is probably not mediated by the nigrotectal pathway.

Animals↗

The superior colliculus and visual neglect in rat and hamster. I. Behavioural evidence.

Lesions of the superior colliculus in rats and hamsters produce a severe visual neglect. Three questions are asked concerning the nature of this impairment. Is the neglect a specific deficit, or part of a general disorder? It appears that the impairment is a relatively specific one, because, for example, collicular animals learn many visual discriminations as fast as controls. This pattern of behaviour leads to the second question. What is tested in neglect tasks but not in discrimination problems? Two answers have been proposed. (a) Orienting responses are required in tests of neglect but not in conventional visual-discrimination tasks. Accordingly, it has been suggested that damage to the superior colliculus interferes specifically with the orienting response. However, analysis of recent evidence indicates that rats and hamsters with collicular damage usually make no detectable response of any kind in tests of neglect, and that in some situations they do not respond to visual stimuli that produce a variety of behaviours in normal animals, such as freezing or fleeing, or activation of the EEG unaccompanied by any gross movement. Collicular neglect cannot therefore be explained solely as a response-specific impairment. (b) The stimuli used on tests of neglect are usually small, moving and presented in the peripheral visual field. In contrast, visual discriminanda are typically large, stationary and can be viewed with the central field. Recent experiments provide direct demonstrations that rats with lesions of the superior colliculus can orient to small flashing lights in central regions of the visual field, but unlike control animals may fail to respond if the lights are made dimmer, or are moved into the periphery. It appears that rats and hamsters with collicular damage fail to register particular kinds of visual stimulus. The final question concerns the nature of this stimulus-specific impairment: Do rats and hamsters with lesions of the superior colliculus neglect certain stimuli because, as has been proposed, they have difficulty in attending to the stimuli, or because they actually are incapable of detecting them? The fragmentary evidence currently available suggests that attentional factors are not important for stimuli that are very small, or that are presented in the far periphery of the visual field: such factors may be more important for large transient stimuli in the central field.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

The superior colliculus and visual neglect in rat and hamster. II. Possible mechanisms.

The observations that removal of the superior colliculus in rats and hamsters produces a striking visual neglect, whereas damage to striate cortex does not, require explanation in terms of the anatomy and physiology of visual pathways in these animals. One proposal is that neglect is produced because the superior colliculus is the only visual structure directly concerned with the production of orienting movements. However, recent behavioural evidence indicates that this mechanism on its own is insufficient: collicular neglect is not confined to orienting movements, but is in part an inability to register particular kinds of visual stimulus. Two additional mechanisms are considered. The superior colliculus receives visual information that the geniculostriate pathway does not. A variety of anatomical and electrophysiological evidence suggests that this is the case. Although the exact nature of the information is unclear, there is some suggestion that the superior colliculus has a stronger representation of the peripheral field than the geniculostriate pathway, and may be more concerned with small transient stimuli throughout the visual field. An intact superior colliculus is essential for normal functioning of the geniculostriate system. Anatomical evidence indicates that there are pathways whereby: (a) visual cortex could use the superior colliculus as an output station; and (b) the superior colliculus could control signals entering or leaving the geniculostriate system, although the nature of the information carried by the pathways is not yet understood. The precise contribution of these two additional mechanisms to collicular neglect remains to be determined. However, it may be conjectured that the first would underly the deficit in stimulus detection that appears to be one component of collicular neglect, whereas the second mechanism might underly an attentional component.

Animals↗

Superior colliculus and visual neglect in rat and hamster. III. Functional implications.

In comparison with the geniculostriate pathway, the retinotectal projection in rat and hamsters appears to emphasize information concerning localized transient stimuli, particularly in the periphery of the visual field. An important question is whether the superior colliculus merely relays this information elsewhere, or instead takes part in its analysis. This question is broken down into two parts. First, what decisions do rats and hamsters have to take concerning localized transient visual stimuli in the periphery? It is suggested that the following decisions are taken: (a) does the stimulus require any response? If the transient is self-produced, or is known on the basis of past experience to predict no important consequence, then it may be ignored; and (b) does the stimulus convey enough information to determine a response, either unlearnt (e.g. attack, flee, freeze) or learnt? If the stimulus appears to warrant some response, but it is not clear which, then it requires investigation. Second, what evidence is there that the superior colliculus participates in any of these decisions? It is argued on general grounds that the involvement of the superior colliculus in investigative orienting necessitates its knowing about the other decisions, since a useful orienting device cannot respond promiscuously to uninteresting or dangerous stimuli. This argument is supported by evidence from stimulation and recording studies, which in addition suggest that the superior colliculus is directly involved in producing a number of responses appropriate to peripheral transients, besides orienting. Thus, one function of the superior colliculus may be to help analyze and take decisions about localized transients in the periphery of the field.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗

Reduced locomotor activity as an acute effect of damage to superior colliculus in rats.

Rats with either electrolytic or radiofrequency lesions of the superior colliculus were tested in an open-field within 24 h of operation. They crossed significantly fewer squares and spent more time motionless then control animals, an effect that disappeared upon retesting 13 days later. Previously reported locomotor hyperactivity thus appears to be a chronic but not an acute effect of collicular damage in rats.

Animals↗

Feeding induced by injections of muscimol into the substantia nigra of rats: unaffected by haloperidol but abolished by large lesions of the superior colliculus.

Intense activation of central dopamine systems has been associated with oral stereotyped behaviour, whereas less intense stimulation of these systems can increase feeding in non-deprived animals. There are several lines of evidence which suggest that the gamma-aminobutyric acid-containing striatonigral and nigrotectal projections are essential pathways mediating dopamine-related oral stereotypy. The present series of experiments was conducted to examine whether the same output route also mediates dopamine-related feeding. In the first experiment it was shown that bilateral injections of a sub-stereotypic dose of muscimol (0.05 nM) into the substantia nigra increased feeding of non-deprived rats. In Experiment II the feeding response was further characterised by demonstrating that food intake was initially suppressed for 30 min after which it was potentiated for 90 min. In Experiment III it was shown that a single dose of haloperidol (0.4 mg/kg), which was adequate to suppress overall food intake, was ineffective in preventing the increase in feeding produced by intranigral muscimol (0.05 nM). In contrast, it was demonstrated in Experiment IV that large lesions of the superior colliculus completely abolished the muscimol-induced increase in feeding. These results suggest that the striatonigral and nigrotectal projections may be important efferent pathways for both the oral stereotypy and the feeding responses linked with central dopamine transmission.

Animals↗

Visual desynchronization of cortical EEG impaired by lesions of superior colliculus in rats.

It is unclear whether rats with lesions of the superior colliculus (SC) neglect visual stimuli because a) they fail to notice the stimuli or b) they notice the stimuli but fail to make specific orienting movements of the eyes and head toward them. To investigate this issue, we used an index of "noticing" that does not involve overt orienting movements, namely, desynchronization of the cortical electroencephalogram (EEG) in drowsy animals. In the first experiment, large collicular lesions with some invasion of surrounding areas severely impaired EEG desynchronization to a brief overhead flash of light but did not significantly affect desynchronization to brief bursts of white noise. No impairment was found after control lesions of cerebral cortex overlying the superior colliculus or of striate cortex. A subsequent experiment found that the visual impairment was still present when lesions were confined to the superior colliculus. It appears that rats with lesions of the superior colliculus can, in certain circumstances, fail to notice visual stimuli and that in rats, the superior colliculus is concerned not only with specific orienting movements to visual stimuli but also with visual desynchronization of the cortical EEG.

Animals↗

Hyperprolactinemia and sexual disturbances among uremic women on hemodialysis.

The investigation of a sample of 99 women on maintenance hemodialysis has shown the presence of sexual disturbances to a great extent: the rate of sexual intercourse and the ability to reach orgasm were significantly lower than in age-matched control women. 80% declared a reduction in their sexual desire and the frequency of intercourse was also lower as compared to the period prior to dialysis. Ageing decreased the sexual activity in both the ill and healthy population, but in uremic patients the sexual activity ended at an earlier age. The patients with hyperprolactinemia reported lower frequencies of intercourse and lower percentages of orgasm than normoprolactinemic ones. The incidence of sexual dysfunction and the role of hyperprolactinemia in this respect were similar to those which are found among male patients on hemodialysis.

Adult↗

Effect of hyperprolactinemia and age on the hypogonadism of uremic men on hemodialysis.

Primary hypogonadism has been commonly reported among uremic men on hemodialysis, characterized by low testosterone levels, increased luteinizing hormone and sometimes follicle-stimulating hormone levels. Little is known about the influence of hyperprolactinemia and age on this hypogonadism. In 149 hemodialysis patients and in 60 healthy subjects the serum levels of testosterone (T), gonadotropins (LH and FSH) and prolactin (PRL) were assessed through radioimmunoassay. Mean +/- SD hormone levels were: T 274 +/- 125 ng/100 ml, lower than controls; LH 44.7 +/- 46.1 mlU/ml and FSH 17.6 +/- 18.4 mIU/ml, both higher than controls. PRL 31.3 +/- 49.4 ng/ml, higher than controls. A positive correlation between LH and FSH, a negative correlation between PRL and both T and LH was found. Moreover T and FSH were correlated with age only in the normoprolactinemic patients. These data suggest: a common damaging mechanism by uremia on both interstitial and tubular structures of the testis; a central antigonadal influence of hyperprolactinemia even if a direct action on the testis cannot be excluded; a worsening action of age on the gonadal function of these patients.

Adult↗

[Desmoid tumors (apropos of a clinical case)].

The authors, starting from a case of desmoid tumour of abdominal wall, they had the opportunity to observe, discuss its possible etiopathogenetic factors, and confirm the validity of operation as the only therapy.

Abdominal Muscles↗

[Spontaneous rupture of the transplanted kidney].

The spontaneous breakage of a kidney is a rare complication which may occur in the first weeks after a transplantation. The cause which can determine it is not yet cleared up, although the Authors think the greatest responsibility for this can be ascribed to rejection. In this work the authors report the experience and casuistry of the Transplantation Centre of Verona.

Adolescent↗

[Lymphocele after renal transplant: considerations based on a clinical case].

The Authors study again the problems of lymphocele in kidney transplantation by showing an interesting clinical case: a lymphocele with smallest size, developing an intensively compressive action on iliac vein. In the light of the experience of 354 transplantations, they discuss the etiopathology and clinics thereof. They particularly emphasize the diagnostical role of echography. Whereas the asymptomatic lymphoceles require no treatments for their trend to be reabsorbed, the symptomatic ones need a quick solution of the compressive effect. Then they consider the therapeutical solutions suggested as an alternative to the interperitoneal marsupialization, which remains the most widely used method.

Adult↗

[New attitudes in the therapy of splenic injuries].

The serious sepses, even deadly, which can follow an operation of splenectomy because of the reduced immunological capacities persuaded the Authors to confirm the necessity to safeguard spleen especially after lesions due to traumata.

Bacterial Infections↗

[Gastric leiomyoma (presentation of 3 clinical cases)].

Gastric leiomyoma represents a rather rare report in abdominal surgery, above all because it very often shows no symptoms. Among the non-epithelial gastric neoplasms, it occupies the second place after lymphoma. After describing its anatomo-pathological aspects and clinical features, the authors report their casuistry, including three observations of such neoplasm, and point out that both the endoscopic inspection and the bioptic abstraction, contextually performed, were not so useful in formulating a sure preoperative diagnosis.

Diagnosis, Differential↗

Head-dipping by rats with lesions of superior colliculus during extended testing in hole-board.

It has previously been shown that rats with large lesions of the superior colliculus fail to head-dip during a 5 min hole-board test. To investigate whether this was a permanent deficit in exploratory behaviour arising from inability to produce the appropriate responses, collicular rats were tested in a hole-board for 60 min or more. The period before their first head-dip (mean 27 min 40 sec) was much longer than for unoperated animals (mean 22 sec), but subsequently the collicular rats showed a pattern of head-dipping that was similar (although not identical) to that of the control rats. It appears that rats with lesions of the superior colliculus are not permanently prevented from exploring the hole-board by inability to produce the required response, but rather that they may have difficulty in discovering certain features of novel environments.

Animals↗