Ectopic ACTH-producing neuroendocrine tumor occurring with large recurrent metastatic pheochromocytoma: a case report.

BACKGROUND: Ectopic ACTH-dependent Cushing syndrome is rarely caused by pheochromocytoma (PCC). Glucocorticoid-regulated positive feedback loops in ACTH and catecholamines were proposed in some similar cases. CASE PRESENTATION: We present here an 80-year-old man who had previously undergone surgery for a left adrenal PCC and newly developed severe hypertension, hypokalemia, and typical Cushingoid manifestations. Investigations revealed hyperglycemia, hypokalemia, and extremely high catecholamines and their metabolites, ACTH and cortisol. Imaging modalities showed a recurrent large left adrenal mass positively visualized with 123I-metaiodobenzylguanidine as well as somatostatin receptor scintigraphy. Surgical interventions were not indicated; thus, metyrapone, phentolamine, and doxazocin were initiated, which successfully controlled his symptoms and biochemical conditions. With the evidence that metyrapone administration decreased ACTH and catecholamine levels, the existence of positive feedback loops was speculated. During the terminal stages of the disease, additional metyrosine treatment successfully stabilized his physiological and biochemical conditions. Upon the patient's death, pathological autopsy was performed. Immunohistochemical analysis indicated that the tumor appeared to be co-positive with tyrosine hydroxylase (TH) as well as ACTH in most tumor cells in both PCC and liver metastasis. Most cells were clearly positive for somatostatin receptor 2 staining in the membrane compartment. The dense immunostaining of ACTH, TH, dopamine-ß-hydroxylase and the large tumor size with positive feedback loops may be correlated with high levels of ACTH and catecholamines in the circulation. CONCLUSIONS: We experienced a case of severe ectopic ACTH producing the largest reported recurrent malignant left PCC with liver metastases that presented positive feedback loops in the ACTH/cortisol and catecholamine/cortisol axes. Clinicians should be aware of the paradoxical response of ACTH on metyrapone treatment and possible steroid-induced catecholamine crisis.

Centronuclear myopathy in mice lacking a novel muscle-specific protein kinase transcriptionally regulated by MEF2.

Myocyte enhancer factor 2 (MEF2) plays essential roles in transcriptional control of muscle development. However, signaling pathways acting downstream of MEF2 are largely unknown. Here, we performed a microarray analysis using Mef2c-null mouse embryos and identified a novel MEF2-regulated gene encoding a muscle-specific protein kinase, Srpk3, belonging to the serine arginine protein kinase (SRPK) family, which phosphorylates serine/arginine repeat-containing proteins. The Srpk3 gene is specifically expressed in the heart and skeletal muscle from embryogenesis to adulthood and is controlled by a muscle-specific enhancer directly regulated by MEF2. Srpk3-null mice display a new entity of type 2 fiber-specific myopathy with a marked increase in centrally placed nuclei; while transgenic mice overexpressing Srpk3 in skeletal muscle show severe myofiber degeneration and early lethality. We conclude that normal muscle growth and homeostasis require MEF2-dependent signaling by Srpk3.

Adsorption and reactions of NO on clean and CO-precovered Ir(111).

Adsorption and reactions of NO on clean and CO-precovered Ir(111) were investigated by means of X-ray photoelectron spectroscopy (XPS), high-resolution electron energy loss spectroscopy (HR-EELS), infrared reflection absorption spectroscopy (IRAS), and temperature-programmed desorption (TPD). Two NO adsorption states, indicative of fcc-hollow sites and atop sites, were present on the Ir(111) surface at saturation coverage. NO adsorbed on hollow sites dissociated to Na and Oa at temperatures above 283 K. The dissociated Na desorbed to form N2 by recombination of Na at 574 K and by a disproportionation reaction between atop-NO and Na at 471 K. Preadsorbed CO inhibited the adsorption of NO on atop sites, whereas adsorption on hollow sites was not affected by the coexistence of CO. The adsorbed CO reacted with dissociated Oa and desorbed as CO2 at 574 K.

Ir/SiO2 as a highly active catalyst for the selective reduction of NO with CO in the presence of O2 and SO2.

Coexisting SO2 considerably enhanced the catalytic activity of Ir/SiO2 for NO reduction with CO in the presence of O2 because of the formation of a cis-type coordinated species of NO and CO to one iridium atom ([formula: see text]), a possible reaction intermediate leading to N2 formation.

Comprehensive study combining surface science and real catalyst for NO direct decomposition.

The catalytic activity of Pd/Al2O3 prepared from various palladium precursors for direct NO decomposition is closely related to the fraction of surface step sites capable of dissociating NO, on the basis of a surface science study using single-crystal model catalyst.