Receptor Binding Affinities and Biological Activities of Linear and Cyclic Melanocortins in B16 Murine Melanoma Cells Expressing the Native MC1 Receptor

Cyclic α-melanocyte-stimulating hormone (α-MSH) analogues produced by disulphide bridging (e.g. [Cys⁴,Cys¹⁰]α-MSH) are known to be almost equipotent to the native hormone in amphibian skin bioassays and as a consequence have been proposed as a paradigm for the active conformation of native MSH at the pigment cell MC1 receptor. However this proposal has been somewhat speculative as there is no published data comparing biological activity of cyclic MSH analogues with data on receptor binding. This study addresses this problem by comparing tyrosinase stimulatory activity with their receptor binding affinity in B16 murine melanoma cells expressing the native MC1 melanocortin receptor. Cyclic [Cys⁴,Cys¹⁰] α-MSH showed almost the same affinity for the MC1 receptor as α-MSH, but the linear analogue [Cys⁴,Cys¹⁰]α-MSH bound less strongly. Both had biological activities similar to that of the natural ligand. Introduction of D-Phe into the ring in position 7 increased both affinity and activity of the cyclic compound. The study suggests that the intrinsic efficacy of cyclic [Cys⁴,Cys¹⁰]α-MSH analogues is similar to native α-MSH. Our studies support the proposal that the cyclic structure serves as a good model for the active conformation of linear α-MSH.     

HOME INTERVENTION WITH PARENTS OF SEVERELY SUBNORMAL, PRESCHOOL CHILDREN AN INTERIM REPORT

A programme of home-based intervention with two groups of pre-school severely subnormal children and their parents has produced apparently contradictory results; frequently visited children after initial superiority over infrequently visited children, later showed a deceleration in intellectual growth. Less frequently visited children conversely showed a rise in performance after an initial decrement. The interpretation is advanced that parents in the latter group were less dependent on the visiting therapist, and more able to take positive action to assist their children, and improve their own situation.     

Intractable pruritus as the presenting symptom of carcinoma of the bronchus: a case report and review of the literature

Patients suffering from intractable pruritus are frequently referred for investigation by the dermatologist. We describe an unusual case in which severe generalized pruritus was the presenting symptom of oat cell carcinoma of the bronchus.     

Delayed Response to Radiofrequency Ablation of Accessory Connections

This article summarizes delayed interruption in anomalous conduction through accessory connections following radiofrequency ablation attempts in three patients. The time course of the delayed interruption in accessory connection conduction suggests that such an effect is unlikely to occur after the first week following unsuccessful radiofrequency ablation.