Neurosurgical aspects and clinical outcomes on the treatment of Cushing disease in pediatric patients: Case series and literature review.

Background: Cushing disease (CD) is a state of hypercortisolism caused by an adrenocorticotropic hormone-(ACTH) producing pituitary adenoma which rarely occurs in pediatric patients. The outstanding features are weight gain and growth retardation. However, the insidious onset and rarity of the disease in children and adolescents often result in delayed diagnosis. Case Description: We present five patients <14 years of age who underwent neurosurgical treatment for CD at the Department of Neurosurgery of a public referral hospital in Lima, Peru. Age at diagnosis ranged from 5.5 to 12.5 years with a history of disease from 9 months to 3.5 years of moderate to severe stunting and obesity, among other features of Cushing syndrome (CS). Although biochemical tests and cerebral imaging were crucial for the diagnosis, confirmation was made by bilateral petrosal sinuous sampling. Regarding treatment, three patients underwent transcranial surgery, one patient underwent endoscopic transsphenoidal surgery, and one patient underwent microscopic transsphenoidal surgery. None of the patients underwent radiotherapy or pharmacological treatment. Only one patient had a recurrence and achieved remission until an endoscopic transsphenoidal approach was performed. Short- and long-term endocrinologic follow-up is also described in detail. Conclusion: CD is a heterogeneous disorder that requires multidisciplinary diagnosis and management. Transsphenoidal selective adenomectomy is the optimal treatment because of its higher remission rates. However, technical and anatomic aspects should be considered in pediatric patients.

The RCSB PDB information portal for structural genomics.

The RCSB Protein Data Bank (PDB) offers online tools, summary reports and target information related to the worldwide structural genomics initiatives from its portal at http://sg.pdb.org. There are currently three components to this site: Structural Genomics Initiatives contains information and links on each structural genomics site, including progress reports, target lists, target status, targets in the PDB and level of sequence redundancy; Targets provides combined target information, protocols and other data associated with protein structure determination; and Structures offers an assessment of the progress of structural genomics based on the functional coverage of the human genome by PDB structures, structural genomics targets and homology models. Functional coverage can be examined according to enzyme classification, gene ontology (biological process, cell component and molecular function) and disease.

A structure-based method for identifying DNA-binding proteins and their sites of DNA-interaction.

A classification model of a DNA-binding protein chain was created based on identification of alpha helices within the chain likely to bind to DNA. Using the model, all chains in the Protein Data Bank were classified. For many of the chains classified with high confidence, previous documentation for DNA-binding was found, yet no sequence homology to the structures used to train the model was detected. The result indicates that the chain model can be used to supplement sequence based methods for annotating the function of DNA-binding. Four new candidates for DNA-binding were found, including two structures solved through structural genomics efforts. For each of the candidate structures, possible sites of DNA-binding are indicated by listing the residue ranges of alpha helices likely to interact with DNA.