Dimensions of clinical medicine: an interclerkship program.

BACKGROUND: During the 3rd year of medical school, clerkships provide essential clinical experiences. However, other aspects of patient care may be overlooked during this critical phase of medical education. Faced with the challenge of integrating "orphan" topics central to effective and compassionate medical practice, medical schools have begun to develop interclerkships or intersessions. DESCRIPTION: The Dimensions of Clinical Medicine (DCM) interclerkship series at Creighton University included evidence-based medicine, sexuality in clinical medicine, palliative care, professionalism, cultural sensitivity/awareness, complementary and alternative medicine, bioterrorism, and clinical ethics. Each interclerkship comprises 2 half-day sessions conducted at the end of each clerkship rotation. EVALUATION: Students approved of the interclerkship format and valued the active learning strategies employed in the course. Many students felt the time allotted for each program was excessive. We describe educational issues and practical concerns that are central to an effective intersession program. CONCLUSION: The interclerkship format is a viable approach for incorporating orphan topics into the clinical curriculum.

Antennulary sensory organs in cyprids of Octolasmis and Lepas (Crustacea: Thecostraca: Cirripedia: Thoracica): a scanning electron microscopic study.

Cypris larvae of the pedunculate barnacles Octolasmis angulata (Poecilasmatidae), Lepas australis, L. pectinata, and Dosima fascicularis (Lepadidae) were studied with scanning electron microscopy, focusing on the sensory setae and the attachment disc on the antennules. The antennules of O. angulata did not exhibit any remarkable trait, but carry the same number of setae as seen in most other thoracicans. The third segment is bell-shaped and quite distinct from the second and its attachment disc is surrounded by a skirt. We found several potential synapomorphies in antennulary morphology between cyprids of the lepadid species but none of them were shared with the cyprids of Octolasmis; the list of unique lepadid characters includes: one additional, preaxial seta on the second segment; multiple similar (up to eight) postaxial setae (PS3) on the third segment, unlike all other thoracicans, where there is only a single PS3; the third segment consists almost entirely of the attachment disc, which is distended and surrounded by two parallel rows of radial setae; on the fourth segment the terminal seta E is diminutive. We found no traits in cyprids of Octolasmis that seem to be adaptations to their attachment site within the branchial chamber of swimming crabs and, in particular, no similarities with cyprids of rhizocephalan barnacles, many of which also attach in the gill chamber. The synapomorphies between cyprids of the lepadid species may be adaptations to their life in the neuston.

Tonic inhibitory role for cAMP in alpha(1a)-adrenergic receptor coupling to extracellular signal-regulated kinases 1/2.

alpha(1a)-Adrenergic receptors (ARs) couple to phosphoinositide hydrolysis, adenylyl cyclase, and mitogen-activated protein kinase (MAPK) pathways. However, the interaction among these signaling pathways in activating extracellular signal-regulated kinase 1/2 (ERK1/2) is not well understood. We investigated the coupling of alpha(1a)-ARs to ERK1/2 in Chinese hamster ovary (CHO)-K1 cells stably transfected with mouse alpha(1a)-ARs, as well as the interaction between ERK1/2 and norepinephrine-induced cAMP accumulation. alpha(1a)-AR activation by norepinephrine increased the cytosolic Ca(2+) concentration and phosphorylated ERK1/2 in a time- and concentration-dependent manner. ERK1/2 phosphorylation was blocked by the MAPK kinase 1/2 inhibitor 2'-amino-3'-methoxyflavone (PD 98059) and the alpha(1)-AR antagonist prazosin. A transient elevation in intracellular Ca(2+) was required for the phosphorylation of ERK1/2; however, activation of protein kinase C did not seem to be required for ERK1/2 phosphorylation. Norepinephrine also stimulated cAMP accumulation in transfected CHO-K1 cells in a concentration-dependent manner via alpha(1a)-ARs, which was blocked by the Ca(2+) chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid. Norepinephrine-induced ERK1/2 phosphorylation was inhibited by the adenylyl cyclase activator forskolin and was enhanced by the adenylyl cyclase inhibitor 9-(tetrahydro-2-furanyl)-9H-purine-6-amine (SQ 22536) and the protein kinase A inhibitor 4-cyano-3-methylisoquinoline. In conclusion, in transfected CHO-K1 cells, alpha(1a)-AR activation activates both phospholipase C and adenylyl cyclase-mediated signaling pathways. alpha(1a)-AR-mediated ERK1/2 phosphorylation was dependent on a rise in intracellular Ca(2+), and this pathway was reciprocally regulated by the concomitant activation of adenylyl cyclase, which inhibits ERK1/2 phosphorylation. Thus, alpha(1a)-AR stimulation of cAMP production may play an important role in regulating ERK1/2 phosphorylation in cell lines and native tissues.

Relationship between alpha(1)-adrenergic receptor-induced contraction and extracellular signal-regulated kinase activation in the bovine inferior alveolar artery.

The endogenous adrenergic agonists norepinephrine (NE) and epinephrine regulate vascular tone by stimulating alpha(1)-adrenergic receptors (ARs) on smooth muscle cells to cause contraction. In addition, alpha(1)-ARs also couple to growth factor pathways, through stimulation of mitogen-activated protein kinases (MAPKs). MAPKs are a family of serine-threonine kinases that include extracellular signal-regulated kinase (ERK) and a variety of other kinases that are able to activate transcription factors when stimulated. We examined alpha(1)-AR stimulation of contraction and ERK activation in the bovine inferior alveolar artery (BIAA), using in vitro contraction studies and Western blotting. Using antagonists selective for individual adrenergic receptor types, we found that only alpha(1)-ARs were coupled to ERK activation and contraction. NE stimulated contraction (EC(50) = 11 microM) and ERK activation (EC(50) = 21 microM) with similar potency. Using alpha(1)-AR subtype-selective antagonists, we identified the alpha(1)-AR subtypes coupled to each response. Affinity values for alpha(1)-AR subtype-selective antagonists were consistent with alpha(1A)-AR-mediated contraction. In contrast, simultaneous treatment with concentrations of these antagonists selective for each alpha(1)-AR subtype (alpha(1A)-, alpha(1B)-, and alpha(1D)-AR) was required to inhibit ERK activation, suggesting that all three alpha(1)-ARs activate ERK in BIAA. Transmural electrical stimulation of BIAA segments resulted in activation of ERK, which was inhibited by the alpha(1)-AR-selective antagonist BE 2254 (2-[[beta-(4-hydroxyphenyl)ethyl]aminomethyl]-1-tetralone). These data suggest that in an intact artery, NE released from sympathetic nerves stimulates alpha(1)-ARs to cause contraction and ERK activation, and that redundancy among subtypes exists for alpha(1)-AR activation of ERK.