International Union of Pharmacology. XXXII. The mammalian calcitonin gene-related peptides, adrenomedullin, amylin, and calcitonin receptors

The calcitonin family of peptides comprises calcitonin, amylin two calcitonin gene-related peptides (CGRPs), and adrenomedullin. The first calcitonin receptor was cloned in 1991. Its pharmacology is complicated by the existence of several splice variants. The receptors for the other members the family are made up of subunits. The calcitonin-like receptor (CL receptor) requires a single transmembrane domain protein, termed receptor activity modifying protein, RAMP1, to function as a CGRP receptor. RAMP2 and -3 enable the same CL receptor to behave as an adrenomedullin receptor. Although the calcitonin receptor does not require RAMP to bind and respond to calcitonin, it can associate with the RAMPs, resulting in a series of receptors that typically have high affinity for amylin and varied affinity for CGRP. This review aims to reconcile what is observed when the receptors are reconstituted in vitro with the properties they show in native cells and tissues. Experimental conditions must be rigorously controlled because different degrees of protein expression may markedly modify pharmacology in such a complex situation. Recommendations, which follow International Union of Pharmacology guidelines, are made for the nomenclature of these multimeric receptors.

An investigation of managerial skills:Implications for personnel policy

This research explores the conceptual basis in adopting a skills approach to management development. The literature reveals a number of development approaches but only a limited appreciation of how the manager does his job i.e. of the skills that he needs. An investigation of managerial skills was conducted with 10 manager s mainly occupying middle and senior positions. The principal source of evidence was the manager's thoughts on what he did and how he did it, although the interviews were supplemented by formal and informal observation. There was also a dialectic value from discussions with other analysts/managers and empathy between analyst and practitioner also played a part. Each manager was invited to comment upon his own skills analysis as a check upon validity. The study supports the view that the manager similar to other skilled practitioners, is conceptually a model builder and operationally a navigator (Singleton 1978b) . The manager variously holds enactive, pictorial, symbolic and hybrid models that enable him to understand his world and act in it. The universal managerial function is decision making and the study presents a preliminary nomenclature in classifying decision processes or perceptual skills. Managerial skills are also reflected in interpersonal interaction where the hallmark is mutual construction and attribution and in 'self-management’ where the requirement is to cope with the inner rather than the outer world. Differences between the managers are most evident in perceptual skills, the more senior manager requiring increasing ability to process abstract information and take account of environmental uncertainty. He will also make greater use of 'off- line’ information. The practical purpose in studying managerial skills is to facilitate the improvement of managerial performance and the implications of the research for training, selection and appraisal are explored.

Classifying clinical decision making:interpreting nursing intuition, heuristics and medical diagnosis

This is the second of two linked papers exploring decision making in nursing. The first paper, 'Classifying clinical decision making: a unifying approach' investigated difficulties with applying a range of decision-making theories to nursing practice. This is due to the diversity of terminology and theoretical concepts used, which militate against nurses being able to compare the outcomes of decisions analysed within different frameworks. It is therefore problematic for nurses to assess how good their decisions are, and where improvements can be made. However, despite the range of nomenclature, it was argued that there are underlying similarities between all theories of decision processes and that these should be exposed through integration within a single explanatory framework. A proposed solution was to use a general model of psychological classification to clarify and compare terms, concepts and processes identified across the different theories. The unifying framework of classification was described and this paper operationalizes it to demonstrate how different approaches to clinical decision making can be re-interpreted as classification behaviour. Particular attention is focused on classification in nursing, and on re-evaluating heuristic reasoning, which has been particularly prone to theoretical and terminological confusion. Demonstrating similarities in how different disciplines make decisions should promote improved multidisciplinary collaboration and a weakening of clinical elitism, thereby enhancing organizational effectiveness in health care and nurses' professional status. This is particularly important as nurses' roles continue to expand to embrace elements of managerial, medical and therapeutic work. Analysing nurses' decisions as classification behaviour will also enhance clinical effectiveness, and assist in making nurses' expertise more visible. In addition, the classification framework explodes the myth that intuition, traditionally associated with nurses' decision making, is less rational and scientific than other approaches.

IUPHAR-DB:the IUPHAR database of G protein-coupled receptors and ion channels

The IUPHAR database (IUPHAR-DB) integrates peer-reviewed pharmacological, chemical, genetic, functional and anatomical information on the 354 nonsensory G protein-coupled receptors (GPCRs), 71 ligand-gated ion channel subunits and 141 voltage-gated-like ion channel subunits encoded by the human, rat and mouse genomes. These genes represent the targets of approximately one-third of currently approved drugs and are a major focus of drug discovery and development programs in the pharmaceutical industry. IUPHAR-DB provides a comprehensive description of the genes and their functions, with information on protein structure and interactions, ligands, expression patterns, signaling mechanisms, functional assays and biologically important receptor variants (e.g. single nucleotide polymorphisms and splice variants). In addition, the phenotypes resulting from altered gene expression (e.g. in genetically altered animals or in human genetic disorders) are described. The content of the database is peer reviewed by members of the International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification (NC-IUPHAR); the data are provided through manual curation of the primary literature by a network of over 60 subcommittees of NC-IUPHAR. Links to other bioinformatics resources, such as NCBI, Uniprot, HGNC and the rat and mouse genome databases are provided. IUPHAR-DB is freely available at http://www.iuphar-db.org. © 2008 The Author(s).

Reply: 'Myopic foveoschisis: An ectatic retinopathy, not a schisis'

Full text: We thank Tsilimbaris et al1 for their comments on the appropriateness of the term ‘myopic foveoschisis’ to describe the condition that is characterized by the separation of neural retina layers associated with high myopia and posterior staphyloma. They have proposed the term ‘myopic ectatic retinopathy’ as a more literal and functionally more accurate descriptor of the condition to avoid the use of the word ‘schisis’, which may be misleading because it is also used to describe other conditions where there is separation of neural retina layers without the presence of staphyloma.2 Using the word ‘ectatic’ for this condition would imply that we are fairly certain about the pathogenesis and mechanistic factors that underlie its development and progression. However, this is not the case, unfortunately, as our review of the literature has shown. There are several theories ranging from vitreous traction to sclerosing changes of retinal vessels to progression of staphylomas as possible etiological factors. Therefore, it is likely to be multifactorial in nature—hence the success reported with different procedures that address either the vitreous traction factor using vitrectomy, peel plus tamponade or the scleral ectasia factor using posterior buckling techniques. In the absence of a good understanding of underlying pathogenesis, it is probably best to use purely descriptive names rather than mechanistic terms. The use of descriptive terms, even though similar, do not necessarily cause confusion as long as they are widely accepted as differentiating terminology, for example, postoperative pseudophakic cystoid macular edema (Irvine–Gass syndrome) vs cystoid macular edema associated with posterior uveitis in a phakic patient. The introduction of too many mechanistic or pathogenetic terms in the absence of clear understating of etiology can in fact cause more confusion, for example, serous chorioretinopathy vs central serous retinopathy vs serous choroidopathy. The confinement to broad descriptive terms can enhance communication and reduce confusion without committing to any presumption about etiology until it is better understood. This approach is probably best illustrated by the recent advances in the understanding of mactel21, a condition initially described and classified, using descriptive nomenclature, by Don Gass as bilateral, idiopathic acquired juxtafoveolar telangiectasis (Group2A) and as distinctly different from unilateral, congenital parafoveolar telangiectasis (Group 1A; Gass,3 pp 504–506 vs 127–128). Finally, it is worthy to note that for myopic foveoschisis associated with a staphyloma that is associated with outer layer macular detachment, Don Gass also descriptively included the additional observation (before the advent of OCT) that the retinal profile was concave rather than convex in shape, thereby differentiating it from rhegmatogenous detachments with recruitment of subretinal fluid that is associated with posteriorly located breaks and macular holes in myopic eyes. References 1.Tsilimbaris MK, Vavvas DG, Bechrakis NE. Myopic foveoschisis: an ectatic retinopathy, not aschisis. Eye 2016; 30: 328–329. 2.Powner MB, Gillies MC, Tretiach M, Scott A, Guymer RH, Hageman GS et al. Perifoveal müller cell depletion in a case of macular telangiectasia type 2. Ophthalmology 2010; 117(12): 2407–2416. 3.Gass DM. Stereoscopic Atlas of Macular Diseases: Diagnosis and Treatment, 4th edn. Mosby-Yearbook: St. Louis, 1997.