Estrogen-related receptor α, the molecular clock, and transcriptional control of metabolic outputs.

Metabolism and circadian rhythms must be closely integrated to support the energetic needs of the organism linked to the daily timing of physiological and behavioral processes. Although components of the molecular clock can directly target some metabolic genes, the control of metabolic clock output is believed to be mediated mostly through the action of transcription factors whose patterns of expression are rhythmic in metabolic tissues. Our recent work has identified the orphan nuclear receptor estrogen-related receptor α (ERRα), a potent effector of metabolic gene networks, as a direct regulator of the molecular clock. Thus, by acting both upstream of and downstream from the molecular clock, ERRα serves as a key transcription factor linking the clock with metabolic control.

Portal vein thrombosis in patients with cirrhosis: does sonographic detection of intrathrombus flow allow differentiation of benign and malignant thrombus?

OBJECTIVE: The objective of our study was to determine if the detection by Doppler sonography of blood flow in portal vein thrombi occurring in patients with cirrhosis could be used to distinguish benign from malignant portal vein thrombi. SUBJECTS AND METHODS: Color and duplex Doppler sonographic examinations were performed in 47 patients with proven cirrhosis and portal vein thrombi. The examinations were directed at the detection of continuous or pulsatile flow within the portal vein thrombi. The nature of the portal vein thrombi was proven histologically in 27 patients and by CT findings and clinical history in 20 patients. The frequency, type, and direction of portal vein thrombus flow was evaluated to determine if there was any correlation with the benign or malignant nature of the portal vein thrombi. RESULTS: Of the 47 patients, 26 had malignant portal vein thrombi and 21 had benign portal vein thrombi. Blood flow was detected in 22 of the malignant and in 15 of the benign portal vein thrombi. The blood flow was pulsatile in 16 malignant and three benign portal vein thrombi and continuous in six malignant and 12 benign portal vein thrombi. The direction of the pulsatile flow in the malignant portal vein thrombi was predominantly (13/16) hepatofugal. All continuous flow in both benign and malignant portal vein thrombi was hepatopetal. The detection of pulsatile flow in portal vein thrombi yielded a 62% sensitivity and 95% specificity for the diagnosis of malignant portal vein thrombus. CONCLUSION: The detection by Doppler sonography of pulsatile flow in portal vein thrombi occurring in patients with cirrhosis is a moderately sensitive but highly specific sign for the diagnosis of malignant portal vein thrombus. However, continuous flow can be detected in benign and malignant portal vein thrombus and is thus not useful in differentiating between the two.

Detection of transjugular intrahepatic portosystemic shunt dysfunction: value of duplex Doppler sonography.

OBJECTIVE: Recent reports have shown that a high percentage of patients with transjugular intrahepatic portosystemic shunts (TIPS) have postprocedural shunt complications, including thrombosis of the stent, stenosis of the stent, or stenosis of the hepatic vein draining the stent. We did a prospective study to determine the utility of Doppler sonography as a screening technique for the detection of these complications. SUBJECTS AND METHODS: From September 1991 to September 1992 we placed TIPS in 45 patients. After the procedure, patients were routinely evaluated with both Doppler sonography and angiography. The sonographic protocol consisted of insonation of the stent, portal vein, and hepatic vein to determine the presence of flow, peak velocity, and direction of flow. The angiograms were evaluated for stenoses of the stent or hepatic vein that caused an increase in the portosystemic pressure gradient greater than 15 mm Hg, increased intrahepatic portal venous filling, retrograde filling of the draining hepatic vein, or opacification of varices. The sonographic findings were statistically evaluated to determine if sonography could demonstrate the complications shown by angiography. RESULTS: Adequate follow-up was obtained in 29 of the 45 patients. Sixteen of the 29 patients had shunt complications that consisted of one stent thrombosis, three stent stenoses, nine hepatic vein stenoses, and three concomitant stenoses of the stent and hepatic vein. Flow was not detected by sonography in the stent of the patient with thrombosis. There was a significant difference (p = .003) between the temporal change in peak stent velocity in patients with stenoses versus those without. Use of a change (increase or decrease) in peak stent velocity greater than 50 cm/sec from the post-TIPS baseline sonogram as the diagnostic criterion for the detection of shunt stenoses resulted in a 93% sensitivity and 77% specificity. Five patients with stenosis had reversed flow in the draining hepatic vein. Only one patient with a stenosis had a peak stent velocity less than 50 cm/sec. CONCLUSION: Our results suggest that Doppler sonography is an excellent noninvasive screening technique for the detection of complications of TIPS. We have found a temporal change in peak stent velocity greater than 50 cm/sec to be a more sensitive sonographic sign of TIPS stenosis than the previously reported low-velocity parameters. Our experience suggests that nearly all complications of TIPS can be detected by using three criteria: (1) no flow for thrombosis, (2) a temporal change in peak stent velocity greater than 50 cm/sec for stent and/or hepatic vein stenosis, and (3) reversed flow in the hepatic vein draining the stent for hepatic vein and, rarely, stent stenosis.

Soft-x-ray projection imaging with a 1:1 ring-field optic.

A molybdenum/silicon multilayer-coated 1:1 ring-field optic with a numerical aperture of 0.0835 is used to carry out soft-x-ray projection imaging with undulator radiation at 12.9 nm. An ideal optic of this type should be able to image 0.1-µm features with a contrast exceeding 90% at this wavelength. The useful resolution of our ring-field optic is experimentally found to be approximately 0.2 µm, probably because of the presence of substrate figuring errors.

Soft-x-ray projection lithography: printing of 0.2-microm features using a 20:1 reduction.

We demonstrate nearly diffraction-limited printing of 0.2-microm features, using soft x rays of approximately 36-nm wavelength. An open-stencil transmission mask with minimum features of 4 microm was imaged by a twentyfold-reduction Schwarzschild-type objective onto silicon wafers coated with various e-beam resists. Implications for soft-x-ray projection lithography are discussed.