Effects of noradrenaline on45Ca2+ efflux from isolated rat islets of Langerhans

Noradrenaline caused a prompt but transient increase in the rate of⁴⁵Ca²⁺ efflux from isolated rat islets of Langerhans perifused in Ca²⁺ depleted medium. The response was modest in size and was unaffected by isosmotic replacement of NaCl with choline chloride or by inclusion of 0.5 mM dibutyryl cAMP in the perifusion medium, suggesting that it was not mediated by Na+: Ca²⁺ exchange nor by lowered cAMP. Despite its effect on⁴⁵Ca²⁺ efflux, noradrenaline treatment did not alter the kinetics of⁴⁵Ca²⁺ efflux in response to the muscarinic agonist, carbamylcholine, nor did it change the magnitude of the response to this agent. Simultaneous introduction of 20 mM glucose with noradrenaline prevented a rise in⁴⁵Ca²⁺ efflux and indeed resulted in inhibition of⁴⁵Ca²⁺ efflux. The data suggest that noradrenaline does not directly activate the mechanisms which regulate Ca²⁺ extrusion from islets cells, and they do not support a primary role for the Ca²⁺ efflux response in mediating adrenergic inhibition of insulin secretion.     

On the applicability of adaptive bioprocess state estimators

This article presents an industrial case study, examining the application of a novel adaptive biomass estimator to an industrial microfungi production process. It is our intention that this contribution should focus upon the implementation issues of the algorithm, in preference to a rigorous theoretical development. The novel algorithm adopted is developed from Adaptive Inferential Estimation studies of Guilandoust and co-workers. The technique utilizes input-output process measurements obtained at different frequencies, thereby providing more frequent estimates of biomass concentration than are otherwise available from off-line laboratory analyses. The algorithm is particularly suited to the biotechnology industry, as it is capable of utilizing irregular assay measurements with varying delays.Although this article demonstrates the encouraging industrial implications of the adaptive algorithm, like all adaptive techniques currently developed, it is restricted by the inability to perform robust on-line system identification. The ultimate selection of a "suboptimal" "fixed parameter" algorithm for on-line implementation, is therefore directly attributable to these inadequacies. Aspects of data acquisition, data pretreatment, and data quality are critical for real process applications, and while some practical approaches are adopted here, many important implementation problems remain unresolved. (c) 1993 John Wiley & Sons, Inc.     

Mapping the diabetes polygene Idd3 on mouse Chromosome 3 by use of novel congenic strains

Development of novel congenic mouse strains has allowed us to better define the location of the diabetogenic locus, Idd3, on Chromosome (Chr) 3. Congenic strains were identified by use of published and newly developed microsatellite markers, their genomes fingerprinted by a rapid, fluorescence-based approach, and their susceptibility to type 1 diabetes evaluated. The maximum interval containing Idd3 is now approximately 4 cM.     

Inhibition of tumor cell invasion by verapamil.

Verapamil, a calcium channel antagonist, inhibits murine B16 melanoma and colon adenocarcinoma C26 tumor metastasis by altering platelet aggregation [Tsuruo, T., et al. (1985) Cancer Chemother. Pharmacol., 14:30-33]. However, the role of calcium homeostasis in regulating several biochemical pathways implicated in other steps of the metastatic cascade suggests that calcium channel antagonists could also inhibit metastasis by other mechanisms. In this report, non-toxic doses of verapamil reversibly decreased human A375M and C8161 melanoma cell invasion and metastasis in a dose-dependent manner. Verapamil reduced cellular invasion and metastases by up to 96% (range 78-96%). Concomitantly, verapamil disrupts microtubule and microfilament organization and inhibits unidirectional cell migration but does not affect cellular adhesion to endothelial monolayers or reconstituted basement membranes. In addition, tumor cells treated with verapamil have a decrease in mRNA of type IV collagenase, a proteinase important in tumor cell degradation of basement membranes. Collectively, these data offer additional evidence regarding the mechanisms of action of verapamil as an anti-metastatic agent.     

Changes in cyclic AMP, adrenylate cyclase and protein kinase levels during the development of embryonic chick skeletal muscle.

The levels of cyclic AMP (cAMP) and activities of adenylate cyclase and protein kinase have been examined in chick skeletal muscle tissue between the 7th and 15th day of its embryonic development. The tissue cAMP levels were found to increase in two main phases; from 8–10 days and from 12–15 days of development. Parallel increases between the 8th and 10th day of development were also found in the basal enzyme activities of both adenylate cyclase and protein kinase. The maximum values of all three parameters coincided with the onset of cell fusion in the tissue. The results are compared with the findings of a similar study carried out on differentiating myoblasts cultured in vitro, and are assessed in terms of the possibility that cAMP levels control the expression of myoblast differentiation.