Opposite effects of phospholipase A2 on [3H]AMPA binding in adult and neonatal membranes.

In the present study, we compared the effect of phospholipase A2 (PLA2) treatment of synaptic membranes from adult and neonatal rats on the characteristics of [3H]AMPA binding sites. Whereas PLA2 treatment of membranes from adult rats produces an increased affinity for [3H]AMPA binding, the same treatment in neonatal rats results in a decrease in the maximal number of binding sites. Since activation of PLA2 has been proposed to play a critical role in the formation of long-term potentiation (LTP), possibly mediated through a modification of the AMPA receptors, the results strengthen the hypothesis that PLA2-induced modification of [3H]AMPA binding sites is an important component of synaptic plasticity.     

Differential effects of specific opioid receptor agonists on rat pup isolation calls.

The possibility was investigated that specific opioid receptor types might selectively alter the production of isolation-induced ultrasonic vocalizations. Intracisternal injections of mu, delta and kappa opioid receptor agonists were administered to isolated 10-day-old rat pups. The mu receptor agonist [D-Ala2-NMe-Phe4-Gly-ol]-enkephalin (DAMGO) and delta receptor agonist [D-Pen2, D-Pen5]-enkephalin (DPDPE) both reduced the rate of isolation-induced ultrasonic calling in the absence of sedation. The kappa receptor agonist U50,488 had the opposite effect, significantly raising the rate of vocalization. Fourteen-day-old pups, with a larger delta receptor population, showed a greater sensitivity to DPDPE than was seen in the younger animals.     

Tetrahydroaminoacridine improves passive avoidance retention defects induced by aging and medial septal lesion but not by fimbria-fornix lesion.

The present study examines whether tetrahydroaminoacridine (THA) can improve the deterioration in passive avoidance (PA) retention performance induced by medial septal (MS) and fimbria-fornix (FF) lesions in young rats or by aging. Retention of young MS-lesioned rats was improved by pretraining injection of THA at 3 mg/kg, but not by THA at 1 mg/kg or by either of the posttraining doses of THA (1 and 3 mg/kg). Pretraining injections of THA at 1 or 3 mg/kg had no effect on the PA retention performance of FF-lesioned rats. Age-induced PA failure was alleviated by pretraining administration of THA at 1 and 3 mg/kg. Posttraining injections of THA (1 or 3 mg/kg) had no effect on PA retention performance of aged rats. These results demonstrate that 1) THA may improve hippocampal cholinergic denervation-induced functional deficits and 2) some of the age-related PA deficits may be due to a cholinergic deficit and can be reversed with THA.     

Evidence that the serotonin agonist, DOI, increases renin secretion and blood pressure through both central and peripheral 5-HT2 receptors

DOI [(+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCI] is a serotonin (5-HT1C/5-HT2) agonist, with potent cardiovascular effects. The purpose of the present studies was to determine the identity and location of the 5-HT receptor subtype(s) mediating the renin and blood pressure responses to DOI. Injection (i.p.) of DOI to conscious male rats elevated plasma renin activity in a dose-dependent manner. The 5-HT1C/5-HT2 antagonist ritanserin completely blocked the DOI-induced increase in plasma renin activity. In order to distinguish the 5-HT2- from the 5-HT1C- mediated effect of DOI, spiperone was administered before DOI. Low doses of spiperone (0.01 and 0.1 mg/kg, s.c.) significantly reduced the renin response to DOI. Because spiperone has a higher affinity for 5-HT2 than 5-HT1C receptors, these data suggest that DOI stimulates renin secretion through 5-HT2 receptors. To separate central from peripheral 5-HT receptors, we injected DOI into rats pretreated with saline or xylamidine, a 5-HT2 antagonist which does not cross the blood-brain barrier. Xylamidine produced a shift to the right and suppression of the maximal effect of DOI on plasma renin activity, suggesting a role for peripheral 5-HT2 receptors in the effect of DOI. On the other hand, i.c.v. administration of DOI, using doses lower than the peripherally effective doses, caused a significant elevation of plasma renin activity at 200 micrograms/kg. These experiments suggest that DOI's elevation of plasma renin activity has both peripheral and central sites of action.(ABSTRACT TRUNCATED AT 250 WORDS)     

Curriculum for musculoskeletal radiology.

Although general suggestions have been made regarding a radiology residency curriculum, no specific list of entities has been offered. Over the past ten years, we have developed a resident-run morning conference in musculoskeletal radiology that is supervised by faculty and covers a specific curriculum. We offer our curriculum as an example that may assist other departments in developing their own curricula.     

Therapy of human cervical carcinoma with monoclonal antibody-Pseudomonas exotoxin conjugates.

Pseudomonas exotoxin A (PE) linked to the F(ab')2 fragment of 1H10, a murine monoclonal antibody recognizing a carbohydrate epitope of a glycoconjugate expressed on the surface of human cervical carcinoma tumor cells, was evaluated for in vitro and in vivo activity. PE can kill cells by ADP-ribosylating elongation factor 2 thus inhibiting protein synthesis. Disulfide- as well as thioether-linked immunotoxins (1H10-PE) killed cervical carcinoma cells in vitro and were 20-160 times more inhibitory to target than to control cells. Cell killing was antibody mediated as demonstrated by the reduction of 1H10-PE growth inhibition to target CaSki cells by free 1H10 F(ab')2. In addition, a control antibody immunotoxin was nontoxic to CaSki cells. Thioether-linked 1H10-PE administered either i.v. or i.p. suppressed the growth of established solid s.c. cervical carcinoma tumors xenografted in nude mice for over 30 days. Treatment with antibody alone or a control immunotoxin had no significant effect on tumor growth. Administration of immunotoxin i.p. was associated with less toxicity than administration i.v., but i.v. injections were more effective at suppressing the growth of established solid tumors.     

Paranasal sinus mucocele in cystic fibrosis

The relationship between cystic fibrosis, nasal polyposis and chronic sinusitis is clearly defined. Mucoceles of the paranasal sinuses, however, are a well-described complication of chronic sinusitis in adults; but they rarely occur in the pediatric age group. We report a three-year-old who presented with epiphora and fullness at the right medial canthus. Computed tomography confirmed a right ethmoid mucocele which was surgically drained, with resolution of symptoms. Approximately 12 other cases of mucoceles have been reported in the pediatric age group. Although many of these patients had recognized cystic fibrosis, some were previously undiagnosed. Only after presentation with a mucocele, did sweat testing reveal their underlying pathology. No pediatric patients in the literature were found with mucoceles and normal sweat tests. Paranasal sinus mucoceles may be diagnostic of cystic fibrosis and may be the presenting sign in some patients.