An Ideal PPAR Response Element Bound to and Activated by PPARα.

Peroxisome proliferator-activated receptor-α (PPARα), a nuclear receptor, plays an important role in the transcription of genes involved in fatty acid metabolism through heterodimerization with the retinoid x receptor (RXR). The consensus sequence of the PPAR response element (PPRE) is composed of two AGGTCA-like sequences directionally aligned with a single nucleotide spacer. PPARα and RXR bind to the 5' and 3' hexad sequences, respectively. However, the precise sequence definition of the PPRE remains obscure, and thus, the consensus sequence currently available remains AGGTCANAGGTCA with unknown redundancy. The vague PPRE sequence definition poses an obstacle to understanding how PPARα regulates fatty acid metabolism. Here we show that, rather than the generally accepted 6-bp sequence, PPARα actually recognized a 12-bp DNA sequence, of which the preferred binding sequence was WAWVTRGGBBAH. Additionally, the optimized RXRα hexad binding sequence was RGKTYA. Thus, the optimal PPARα/RXRα heterodimer binding sequence was WAWVTRGGBBAHRGKTYA. The single nucleotide substitution, which reduces binding of RXRα to DNA, attenuated PPARα-induced transcriptional activation, but this is not always true for PPARα. Using the definition of the PPRE sequence, novel PPREs were successfully identified. Taken altogether, the provided PPRE sequence definition contributes to the understanding of PPARα signaling by identifying PPARα direct target genes with functional PPARα response elements.

"Hands-Free" continuous transthoracic monitoring of pericardiocentesis using a novel ultrasound transducer.

BACKGROUND: Pericardiocentesis can be monitored with a hand-held transducer. The purpose of this study was to assess the feasibility of monitoring pericardiocentesis using a novel ultrasound transducer, which can be attached to the chest wall, developed in our laboratory (CONTISON). METHODS: We studied nine patients with large pericardial effusions. The 2.5-MHz transducer is spherical in its distal part and mounted in an external housing to permit steering in 360 degrees. The external housing is attached to the chest wall using an adhesive patch. The CONTISON transducer was placed at the cardiac apex and an apical four-chamber view obtained. Pericardiocentesis was performed from the subcostal position. The pericardial effusion was continuously imaged. Mitral inflow velocity signals were recorded before and after pericardiocentesis. When fluid was first obtained, 50 mL of fluid were discarded after which 5 mL of agitated saline was injected through the needle. RESULTS: In the first patient the pericardiocentesis needle was seen in the left ventricular cavity. Saline injection produced a contrast effect in the left ventricle. The needle was gradually withdrawn until contrast was seen in the pericardial sac. A total of 1100 mL was removed without further complications. The second patient had clear fluid followed by blood stained aspirate. The echocardiogram revealed gradual appearance of granular echoes within the pericardial sac, suggestive of intrapericardial clot that was subsequently surgically evacuated. In the remaining seven patients, agitated saline produced a contrast effect in the pericardial sac indicative of proper needle position. Mitral flow velocity paradoxus was noted in five patients, and it resolved after pericardiocentesis in four patients. No adjustment of the transducer was required. CONCLUSION: The CONTISON transducer permitted continuous monitoring of pericardiocentesis. This technique could potentially facilitate pericardiocentesis.