(65/181) Growth hormone therapy in children and adults.

Growth hormone (GH) is a polypeptide hormone, secreted by somatotropic cells of the anterior part of the hypophysis. Its application in therapy, first limited to GH deficient children, has now been widened to various other clinical conditions, not necessarily related to short stature. Clinical trials conducted in recent years have proved the safety of its administration in both children and adults. The efficacy of this form of therapy varies, according to different authors, from enthusiastic data to very critical opinions. For many pediatric diseases, such as GH deficiency or Turner syndrome, GH is regarded by many experts, despite the high costs of the therapy, as the first-line treatment. Mounting evidence suggests that GH is safe and effective also in children with chronic renal failure and cystic fibrosis. Recently, it has also been administered to adults with GH deficiency and short bowel syndrome. The aim of this paper is to summarize the current data on GH administration in modern pharmacotherapy. In this paper we have included the results of the recently published studies and discussed not commonly known indications for GH therapy, as well as its experimental administration in both children and adults.  (+info)

(66/181) Shp2 knockdown and Noonan/LEOPARD mutant Shp2-induced gastrulation defects.

Shp2 is a cytoplasmic protein-tyrosine phosphatase that is essential for normal development. Activating and inactivating mutations have been identified in humans to cause the related Noonan and LEOPARD syndromes, respectively. The cell biological cause of these syndromes remains to be determined. We have used the zebrafish to assess the role of Shp2 in early development. Here, we report that morpholino-mediated knockdown of Shp2 in zebrafish resulted in defects during gastrulation. Cell tracing experiments demonstrated that Shp2 knockdown induced defects in convergence and extension cell movements. In situ hybridization using a panel of markers indicated that cell fate was not affected by Shp2 knock down. The Shp2 knockdown-induced defects were rescued by active Fyn and Yes and by active RhoA. We generated mutants of Shp2 with mutations that were identified in human patients with Noonan or LEOPARD Syndrome and established that Noonan Shp2 was activated and LEOPARD Shp2 lacked catalytic protein-tyrosine phosphatase activity. Expression of Noonan or LEOPARD mutant Shp2 in zebrafish embryos induced convergence and extension cell movement defects without affecting cell fate. Moreover, these embryos displayed craniofacial and cardiac defects, reminiscent of human symptoms. Noonan and LEOPARD mutant Shp2s were not additive nor synergistic, consistent with the mutant Shp2s having activating and inactivating roles in the same signaling pathway. Our results demonstrate that Shp2 is required for normal convergence and extension cell movements during gastrulation and that Src family kinases and RhoA were downstream of Shp2. Expression of Noonan or LEOPARD Shp2 phenocopied the craniofacial and cardiac defects of human patients. The finding that defective Shp2 signaling induced cell movement defects as early as gastrulation may have implications for the monitoring and diagnosis of Noonan and LEOPARD syndrome.  (+info)

(67/181) Deletion of Ptpn11 (Shp2) in cardiomyocytes causes dilated cardiomyopathy via effects on the extracellular signal-regulated kinase/mitogen-activated protein kinase and RhoA signaling pathways.

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(68/181) Diverse driving forces underlie the invariant occurrence of the T42A, E139D, I282V and T468M SHP2 amino acid substitutions causing Noonan and LEOPARD syndromes.

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(69/181) Noonan syndrome-associated SHP-2/Ptpn11 mutants enhance SIRPalpha and PZR tyrosyl phosphorylation and promote adhesion-mediated ERK activation.

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(70/181) Long-term GH treatment improves adult height in children with Noonan syndrome with and without mutations in protein tyrosine phosphatase, non-receptor-type 11.

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(71/181) Phosphatase-defective LEOPARD syndrome mutations in PTPN11 gene have gain-of-function effects during Drosophila development.

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(72/181) Multiple giant cell lesions in patients with Noonan syndrome and cardio-facio-cutaneous syndrome.

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