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T M Connor

Publications and source records attributed to T M Connor.

9 recordsLinked to original sources
PubMed2001

Involvement of the central nucleus of the amygdala and nucleus accumbens core in mediating Pavlovian influences on instrumental behaviour.

Pavlovian conditioned cues exert a powerful influence on instrumental actions directed towards a common reward, this is known as Pavlovian-to-instrumental transfer (PIT). The nucleus accumbens (NAcc) has been hypothesized to function as an interface between limbic cortical structures required for associative conditioning, like the amygdala, and response mechanisms through which instrumental behaviour can be selected and performed. Here we have used selective excitotoxic lesions to investigate the involvement of subnuclei of the amygdala as well as the core and shell regions of the nucleus accumbens on PIT in rats. Within the amygdala, selective lesions of the central nucleus (CeN), but not of the basolateral nucleus (BLA), abolished the PIT effect. In addition, selective lesions of the NAcc core, but not the NAcc shell, also abolished PIT. None of the lesions impaired the acquisition of Pavlovian food cup approaches or instrumental responding itself. These data demonstrate that the CeN and NAcc core are central components of the neural system mediating the impact of Pavlovian cues on instrumental responding. We suggest that this effect may depend upon the regulation of the dopaminergic innervation of the NAcc core by projections from the CeN to the ventral tegmental area.

Amygdala↗
PubMed1997

bax-deficiency promotes drug resistance and oncogenic transformation by attenuating p53-dependent apoptosis.

Inactivation of p53-dependent apoptosis promotes oncogenic transformation, tumor development, and resistance to many cytotoxic anticancer agents. p53 can transcriptionally activate bax, a bcl-2 family member that promotes apoptosis. To determine whether bax is required for p53-dependent apoptosis, the effects of bax deficiency were examined in primary fibroblasts expressing the E1A oncogene, a setting where apoptosis is dependent on endogenous p53. We demonstrate that bax can function as an effector of p53 in chemotherapy-induced apoptosis and contributes to a p53 pathway to suppress oncogenic transformation. Furthermore, we show that additional p53 effectors participate in these processes. These p53-controlled factors act synergistically with Bax to promote a full apoptotic response, and their action is suppressed by the Bcl-2 and E1B 19K oncoproteins. These studies demonstrate that Bax is a determinant of p53-dependent chemosensitivity and illustrate how p53 can promote apoptosis by coordinating the activities of multiple effectors.

Animals↗
PubMed1996

p53 modulation of anchorage independent growth and experimental metastasis.

Death in circulation is one of the natural barriers preventing dissemination of tumor cells and formation of metastases. One of the negative factors acting in circulation is the loss of cell contact with natural substrate which can be imitated in vitro by the incubation of cells in suspension or in semi-solid media. Normal mouse fibroblasts (MEFs) stay viable in suspension and undergo p53-independent G1 growth arrest. Transformation with Ela and ras oncogenes leads to the abrogation of this arrest and to the p53-dependent apoptosis occurring in G1 phase of the cell cycle. Suppression of apoptosis by p53 gene knock-out, transduction of dominant negative p53 mutant or bcl-2 prevents death in suspension and greatly induces frequency of colony formation in semi-solid media. The ability of cells to undergo apoptosis does not correlate with their tumorigenicity in nude mice but does correlate with their ability to survive in lungs of intravenously injected mice and to form experimental metastases. We suggest that abrogation of a p53-mediated apoptosis facilitates experimental metastasis by promoting survival of tumor cells in circulation.

Animals↗
PubMed1981

L-5-Hydroxytryptophan-induced drinking in rats: possible mechanisms for induction.

Administration of L-5-hydroxytryptophan (25 mg/kg body weight, SC) to female rats resulted in copious drinking. The dipsogenic response to administration of L-5-hydroxytryptophan (5-HTP) was blocked by propranolol (6 mg/kg body weight, IP), a beta-adrenergic antagonist, and captopril (35 mg/kg body weight, IP), an angiotensin converting enzyme inhibitor. In addition, clonidine (12.5 and 25 microgram/kg body weight, IP), a central alpha-adrenergic agonist known to inhibit renin release, attenuated drinking during 1, 2 and 3 hours after 5-HTP was administered. These results suggest that 5-HTP-induced drinking is mediated by way of the renin-angiotensin system. Haloperidol (150 microgram/kg body weight, IP), a dopaminergic antagonist, also attenuated the dipsogenic response to administration of 5-HTP. In addition, incremental reductions in 5-HTP-induced drinking with increasing doses of spiperone (37.5 to 150 microgram/kg body weight, IP), a more potent dopaminergic antagonist, were demonstrated. Thus, the dipsogenic response to administration of 5-HTP to rats is dependent on both the renin-angiotensin system and an intact dopaminergic pathway.

5-Hydroxytryptophan↗
PubMed1981

A comparison of coarctation resection and patch angioplasty using postexercise blood pressure measurements.

Postexercise arm-to-leg blood pressure gradients were measured in 31 patients to determine the effectiveness of two surgical techniques for treating coarctation of the aorta. The arm-to-leg postexercise mean systolic blood pressure gradient was 29 mm Hg lower in 13 patients treated with Dacron patch angioplasty than in 18 patients whose coarctation was resected (p less than 0.01). Some patients with high postexercise gradients after coarctation resection had a reduced proximal aortic lumen by angiography. The results of this study indicate that Dacron patch angioplasty is the method of choice for effectively reducing postexercise systolic pressure gradients in patients with coarctation and hypoplasia of the aortic isthmus.

Adolescent↗
PubMed1979

Evaluation of persistent coarctation of aorta after surgery with blood pressure measurement and exercise testing.

In 16 patients with coarctation of the aorta blood pressure in the arms and legs was measured before and after exercise using a treadmill and the Bruce protocol to achieve a standardized level of exercise. Three patients had had no previous operation; 13 had had a previous surgical repair of the coarctation. Three patients were studied both before and after operation. Two of the 13 patients studied postoperatively were found to have significant residual coarctation on the basis of a postexercise arm to leg pressure gradient that had not been appreciated on routine postoperative examination, and one of these patients was found to have residual coarctation after his second operation. One patient not operated on was believed to have mild coarctation of no clinical significance. Eleven of the 13 patients previously operated on (85%) were found to have had a satisfactory repair. A postexercise arm to leg systolic blood pressure gradient of more than 35 mm Hg after repair of coarctation of the aorta is suggested as an indication for recatheterization.

Adolescent↗
PubMedDate not supplied

Dipsogenic effect of L-5-hydroxytryptophan in rats.

The precursor of serotonin, l-hydroxytryptophan (5HTP), is a potent dipsogen in the rat. Peripheral administration of increasing doses of this compound increased water intake in a dose-dependent fashion. Peripheral administration of other analogs of tryptophan, including d-tryptophan, l-tryptophan and acetyltryptophan, failed to affect water intake at a dose at which 5HTP induced maximal drinking (25 mg/kg, SC). The dipsogenic effect of melatonin, one of the metabolites of serotonin, was also tested. At any of 6 different doses (0.5 to 50 mg/kg, SC), melatonin failed to affect water intake in the rat. The mechanism by which 5HTP induces drinking is not known with certainty but could involve its conversion to serotonin, a known dipsogenic agent.

5-Hydroxytryptophan↗