The cDNA that encodes the rabbit calcitonin receptor was cloned by screening a rabbit osteoclast library. Reverse transcription-polymerase chain reaction amplification of calcitonin receptor sequences from rabbit osteoclast RNA yielded cDNAs that encode two isoforms of the calcitonin receptor. One isoform is homologous to the C1a isoform previously identified in multiple cell types and species, while the second, designated CTR⌬e13, is a previously unidentified isoform that is apparently generated by alternative splicing during mRNA processing that deletes exon 13, resulting in the absence of 14 amino acids in the predicted seventh transmembrane domain. Expression of mRNA transcripts encoding the two isoforms varies in a tissuespecific manner, with CTR⌬e13 accounting for less than 15% of the total calcitonin receptor mRNA in osteoclasts, kidney, and brain, but comprising at least 50% of the transcripts in skeletal muscle and lung. The two isoforms were expressed, and the ligand binding and signal transduction properties were characterized. Deletion of the residues in the seventh transmembrane domain in CTR⌬e13 reduced the binding affinity for salmon and human calcitonin by more than 10-fold and approximately 2-fold, respectively, resulting in a receptor that failed to discriminate between the two forms of calcitonin. Both isoforms activated adenylyl cyclase, with EC 50 values consistent with the difference in ligand affinities. In contrast, only the C1a isoform, but not the CTR⌬e13 isoform, activated phospholipase C. Thus, while the CTR⌬e13 remains active despite the deletion of a significant portion of its seventh transmembrane domain, it has significantly altered ligand recognition and signal transduction properties. Calcitonin (CT)1 is a 32-amino acid peptide hormone that acts to reduce serum calcium levels by inhibiting bone resorption and promoting renal calcium excretion. Besides this hypocalcemic effect, CT modulates the renal transport of water and several ions other than calcium, and acts on the central nervous system to induce analgesia, anorexia, and gastric secretion (1). The CT receptor (CTR) belongs to a family of G protein-coupled peptide receptors that includes receptors for parathyroid hormone/parathyroid hormone-related peptide, secretin, vasoactive intestinal peptide, growth hormone-releasing hormone, glucagon, glucagon-like peptide, pituitary adenylyl cyclase-activating peptide, corticotropin-releasing factor, and calcitonin gene-related peptide (2-4).

BackgroundWound healing is a complex biologic process that involves the integration of inflammation, mitosis, angiogenesis, synthesis, and remodeling of the extracellular matrix. However, some wounds fail to heal properly and become chronic. Although some simulated chronic wound models have been established, an efficient approach to treat chronic wounds in animal models has not been determined. The aim of this study was to develop a modified rat model simulating the chronic wounds caused by clinical radiation ulcers and examine the treatment of chronic wounds with adipose-derived stem cells.ResultsSprague–Dawley rats were irradiated with an electron beam, and wounds were created. The rats received treatment with adipose-derived stem cells (ASCs), and a wound-healing assay was performed. The wound sizes after ASC treatment for 3 weeks were significantly smaller compared with the control condition (p < 0.01). Histological observations of the wound edge and immunoblot analysis of the re-epithelialization region both indicated that the treatment with ASCs was associated with the development of new blood vessels. Cell-tracking experiments showed that ASCs were colocalized with endothelial cell markers in ulcerated tissues.ConclusionsWe established a modified rat model of radiation-induced wounds and demonstrated that ASCs accelerate wound-healing.

While it is well established that adenylyl cyclase and phospholipase C-␤ are two proximal signal effectors for the calcitonin receptor, the more distal signaling pathways are less well characterized. G protein-coupled receptors can activate Erk1/2 by G s -, G i -, or G q -dependent signaling pathways, depending on the specific receptor and cell type examined. Since the calcitonin receptor can couple to all three of these G proteins, the ability of calcitonin to activate Erk1/2 was investigated. Calcitonin induced time-and concentration-dependent increases in Shc tyrosine phosphorylation, Shc-Grb2 association and Erk1/2 phosphorylation and activation in a HEK 293 cell line that stably expresses the rabbit calcitonin receptor C1a isoform. Pertussis toxin, which inactivates G i , and calphostin C, a protein kinase C inhibitor, each partially inhibited calcitonin-induced Shc tyrosine phosphorylation, Shc-Grb2 association, and Erk1/2 phosphorylation. In contrast, neither forskolin nor H89, a protein kinase A inhibitor, had a significant effect on basal or calcitonin-stimulated Erk1/2 phosphorylation. Our results suggest that the calcitonin receptor induces Shc phosphorylation and Erk1/2 activation in HEK293 cells by parallel G i -and PKC-dependent mechanisms. The calcitonin-induced elevation of cytosolic free Ca 2؉ was required for Erk1/2 phosphorylation, since preventing any change in cytosolic free Ca 2؉ by chelating both cytosolic and extracellular Ca 2؉ abolished the response. However, the change in Ca 2؉ that is induced by calcitonin is not sufficient to account for the calcitonin-induced Erk1/2 phosphorylation, since treatment with 100 nM ionomycin or 10 M thapsigargin, each of which induced elevations of Ca 2؉ comparable to those induced by calcitonin, induced significantly less Erk1/2 phosphorylation than that induced by calcitonin. Erk1/2 may have important roles as downstream effectors mediating cellular responses to calcitonin stimulation.

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Aim: Attention-deficit-hyperactivity disorder (ADHD) continues to be among the most frequently missed of psychiatric diagnoses in adults because its presentation in adulthood so often mimics those of better-known disorders. The aim of the present study was to examine the relationship between ADHD symptoms, depression/anxiety symptoms, and life quality in young men.Methods: Nine hundred and twenty-nine draftees into the Taiwanese army completed the Adult ADHD Self-Report Scale (ASRS), the World Health Organization (WHO) Quality of Life-Brief Version, the Epworth Sleepiness Scale, the second edition of the Beck Depression Inventory, and the Beck Anxiety Scale. Based on high ASRS scores, a total of 328 adults (35.3%) were identified as having ADHD: 65 (7.0%) with definite ADHD and 263 (28.3%) with probable ADHD. Results:The 328 subjects in the ADHD group had more severe depressive, anxiety symptoms and daytime sleepiness, and had poorer quality of life than the 601 controls (all P < 0.05).Conclusions: ADHD should be included in the differential diagnosis for young men presenting with anxiety, depression, daytime sleepiness, and poor quality of life.Key words: anxiety, attention-deficit-hyperactivity disorder, depression, quality of life.A TTENTION-DEFICIT-HYPERACTIVITY DISOR-DER (ADHD), which affects between 3% and 10% of the school-age population 1 and 4% of the general population, 2 is a major risk factor for many types of comorbid psychopathology.2-5 Thirty-three percent of childhood patients retain the full ADHD diagnosis into adulthood, and 66% have a partial ADHD diagnosis with moderate persistence of the symptoms of impairment. 3Disorders that co-occur with ADHD have spawned an extensive body of literature. 2,[6][7][8][9][10][11][12][13][14][15][16] In addition, ADHD itself continues to be mistaken for other disorders, 3 especially in adults. ADHD is often accompanied by characteristics not explicitly associated with the current criteria for ADHD as specified in DSM-IV. Although DSM-IV notes that approximately half of all clinic-referred children with ADHD also have oppositional-defiant or conduct disorders (ODD/CD) and also mentions its frequent association with mood disorders, anxiety disorders, learning disorders, and communication disorders, it does not comprehensively describe the clinical presentation of these cases. As a result, most physicians are left to sort out an often bewilderingly complex array of