alpha-Conotoxin ImI exhibits subtype-specific nicotinic acetylcholine receptor blockade: preferential inhibition of homomeric alpha 7 and alpha 9 receptors

Through a study of cloned nicotinic receptors expressed in Xenopus oocytes, we provide evidence that alpha-conotoxin ImI, a peptide marine snail toxin that induces seizures in rodents, selectively blocks subtypes of nicotinic acetylcholine receptors. alpha-Conotoxin ImI blocks homomeric alpha 7 nicotinic receptors with the highest apparent affinity and homomeric alpha 9 receptors with 8-fold lower affinity. This toxin has no effect on receptors composed of alpha 2 beta 2, alpha 3 beta 2, alpha 4 beta 2, alpha 2 beta 4, alpha 3 beta 4, or alpha 4 beta 4 subunit combinations. In contrast to alpha-bungarotoxin, which has high affinity for alpha 7, alpha 9, and alpha 1 beta 1 gamma delta receptors, alpha-conotoxin ImI has low affinity for the muscle nAChR. Related Conus peptides, alpha-conotoxins MI and GI, exhibit a distinct specificity, strictly targeting the muscle subtype receptor but not alpha 7 or alpha 9 receptors. alpha-Conotoxins thus represent selective tools for the study of neuronal nicotinic acetylcholine receptors.     

Development of the enkephalin-, neurotensin- and somatostatin-like (ENSLI) amacrine cells in the chicken retina

The development of the enkephalin-, neurotensin- and somatostatin-like immunoreactive (ENSLI) amacrine cells in the chicken retina has been investigated by radioimmunoassay (RIA) and immunocytochemistry (ICC). By RIA, enkephalin-like immunoreactivity (ENK-LI) was detected at embryonic day (E) 5 at only very low levels, which gradually increased until E17. From E18 to E21, there was a relatively rapid increase in ENK-LI levels, and just after hatching, there was a very steep rise. By ICC, the cell bodies of the ENSLI amacrine cells were first detected in the inner nuclear layer on E18, with no immunostaining in the inner plexiform layer (IPL). On E21, more cells were detected and processes in the IPL were visible, but detailed arborisations were not clear. On postnatal day (P) 1, the ENSLI amacrine cells showed a morphology similar to that in mature retina in both the density of cell bodies and the ramification pattern of processes. Antibodies to neurotensin and somatostatin revealed a similar developmental pattern. Thus, the three peptides appear to follow a similar developmental pattern in the ENSLI amacrine cells, suggesting that the three peptides respond similarly to developmental stimuli, just as they are released in parallel in response to physiological stimulation from mature ENSLI amacrine cells. After hatching, higher levels of ENK-LI were detected by RIA and more ENSLI amacrine cell bodies and processes were detected by ICC in animals kept in the light than in those kept in the dark. In retinas kept in the light for 12 h, it was found that immunoreactive processes in the IPL formed strongly stained patches, but this was not observed in retinas kept in the dark for 12 h.     

The incidence, morbidity, and mortality of surgical procedures after orthotopic heart transplantation

OBJECTIVE: The authors present their experience with patients having undergone orthotopic heart transplantation (OHT) in whom surgical conditions subsequently developed that required operative intervention. The incidence, morbidity, and mortality of these procedures are reported. SUMMARY BACKGROUND DATA: Several studies have evaluated the management options of biliary tract disease after OHT. Multiple reports of patients having undergone OHT who subsequently underwent peripheral vascular reconstructions, plastic reconstructive, and thoracic procedures also have been published. METHODS: A chart review of 349 patients who underwent OHT between 1985 and 1996 was conducted to identify surgical procedures that were required in the post-transplant period. Their outcomes are reported. RESULTS: Of 349 patients who underwent OHT, conditions requiring 94 surgical procedures developed in 54 patients (15%). Biliary tract disease developed in 17 patients (5%) who required cholecystectomy, 2 of the 5 patients with acute cholecystitis died. Eight patients (2%) underwent orthopedic procedures with no operative mortality. Flap advancements for sternal wound infections were performed in five patients and four deaths occurred. Seventeen thoracic procedures were performed in 11 patients with an overall mortality of 45%. Twenty-one vascular procedures were performed on 17 patients with 1 delayed death due to a malignancy. Seven patients underwent procedures of the colon and rectum with no mortality. Seven patients underwent repair of inguinal or incisional hernias with no mortality. Various infections occurred with one resultant death after operative intervention. Six procedures were performed for diseases of the small intestine with no resultant mortalities. CONCLUSIONS: Patients having undergone OHT and chronic immunosuppression are at increased risk of having complications develop from infection. Acute cholecystitis and sternal wound infection caused an inordinate risk of complications and death. Malignancies developed in four patients who required surgical intervention. A heightened awareness of coexisting peripheral vascular disease in patients transplanted for ischemic cardiomyopathy should exist. Close screening before surgery and surveillance after surgery to identify risk factors for infection and vascular disease and to screen for malignancies are essential.