The sterol-sensing endoplasmic reticulum (ER) membrane protein TRC8 hampers ER to Golgi transport of sterol regulatory element-binding protein-2 (SREBP-2)/SREBP cleavage-activated protein and reduces SREBP-2 cleavage.

TRC8 (translocation in renal cancer from chromosome 8) is an intrinsic protein of the endoplasmic reticulum that contains a sterol-sensing domain and a RING finger motif encoding an E3 ubiquitin ligase. Here we show that TRC8 overexpression hinders sterol regulatory element-binding protein-2 (SREBP-2) processing, thereby reducing SREBP-2 target gene expression, TRC8 depletion has the opposite effect. Mutation analyses of TRC8 reveal that the ubiquitin ligase activity is dispensable for these effects. Activating transcription factor 6 (ATF6) is also processed in the Golgi by the same two proteases as those for SREBP, but ATF6 processing is not affected by TRC8. TRC8 is capable of binding both SREBP-2 and SREBP cleavage-activated protein (SCAP), thereby forming a TRC8.SREBP-2.SCAP complex. This complex formation hampers the interaction between SCAP and Sec24, one of the COPII proteins that are involved in SREBP-2 transport to the Golgi, thereby reducing SREBP-2 cleavage. TRC8 conjugated by ubiquitin is unstable, whereas the mutant TRC8, lacking the E3 ubiquitin ligase activity and only slightly modified by ubiquitin, is quite stable. TRC8 becomes stable when cells are cultured with a proteasome inhibitor or under a lipoprotein-depleted condition. Lipoprotein depletion impairs ubiquitination of TRC8. Taken together, TRC8 is a novel sterol-sensing endoplasmic reticulum membrane protein that hinders SREBP-2 processing through interaction with SREBP-2 and SCAP, regulating its own turnover rate by means of its E3 ubiquitin ligase activity.

Usefulness of F-18 FDG-PET in a long-term hemodialysis patient with renal cell carcinoma and pheochromocytoma.

A patient who had been on long-term hemodialysis (HD) was diagnosed as having renal cell carcinoma (RCC) and pheochromocytoma. Abdominal computed tomography scanning demonstrated a right renal mass and a right adrenal mass, whereas positron emission tomography (PET) using F-18 fluorodeoxyglucose (FDG) revealed increased accumulation in both the renal and adrenal masses. FDG-PET is useful for detecting RCC in HD patients because FDG is not excreted in the urine, but it is difficult to distinguish pheochromocytoma from an adrenal metastasis by this imaging method.

Subpial schwannoma of the cervical spinal cord mimicking an intramedullary tumor.

We report a rare case of a subpial schwannoma of the cervical cord mimicking an intramedullary tumor in a 65-year-old woman. The magnetic resonance imaging findings are presented and discussed.

Retrospective review: usefulness of a number of imaging modalities including CT, MRI, technetium-99m pertechnetate scintigraphy, gallium-67 scintigraphy and F-18-FDG PET in the differentiation of benign from malignant parotid masses.

OBJECTIVE: The aim of this study is to evaluate an imaging approach using computed tomography (CT), magnetic resonance imaging (MRI), technetium-99m pertechnetate scintigraphy (99mTc pertechnetate scintigraphy), gallium-67 scintigraphy (67Ga scintigraphy) and fluorine-18 fluorodeoxyglucose positron emission tomography (18F-FDG PET). MATERIAL AND METHODS: We reviewed retrospectively 59 patients with parotid masses. CT, MRI, 67Ga scintigraphy, 99mTc pertechnetate scintigraphy, and 18F-FDG PET were performed. RESULTS: All of the benign tumors had smooth margins on CT and MRI. Patients with inflammatory lesions and malignant lesions showed well-defined margins or ill-defined margins. All Warthin's tumors showed high technetium accumulation. Many of malignant tumors showed high FDG accumulation. Both pleomorphic adenomas and Warthin's tumors showed high accumulation in some cases on 18F-FDG PET. Among 15 patients with pleomorphic adenoma, 14 patients showed marked hyperintensity relative to CSF on T2-weighted images and partial enhancement on contrast-enhanced T1-weighted images. Combination of several imaging modarity offered usefulness of differential diagnosis for parotid masses. CONCLUSION: An efficient combination of imaging methods may be helpful for achieve the correct diagnosis.

Accumulation of glucose in keloids with FDG-PET.

OBJECTIVE: Glucose metabolism has not been investigated in human (in vivo) keloids. In the present study, we performed positron emission tomography (PET) with fluorine-18-fluorodeoxyglucose (FDG) to examine glucose metabolism in keloids. MATERIALS AND METHODS: Five patients (2 men and 3 women) with typical keloids having a thickness of more than 5 mm were studied. HEADTOME-IV SET-1400W-10 (Shimadzu, Tokyo, Japan) was employed for PET studies. Transmission scanning was performed on each patient. After fasting for more than 4 hours, the patients were injected intravenously with FDG 185-370 (MBq) following each transmission scan. Emission scans were performed 40-55 min after injection. For quantitative evaluation, the regions of interest (Circles ROIs: 6 mm in diameter) were placed on all the keloid lesions and surrounding tissues, and then their standardized uptake value (SUV = the tissue concentration/the activity injected per body weight) was calculated. RESULTS: FDG was defined as showing the accumulation in keloids when its uptake was relatively higher in the keloid than that in the surrounding tissue. The SUV of the keloids ranged from 1.0 to 2.74, with a mean of 1.79. CONCLUSION: FDG-PET was performed in 5 patients with keloids and low-grade accumulation of FDG was observed in all lesions. This indicated that glucose metabolism was accelerated in keloids.

Diffusion-weighted MR imaging in patients with phenylketonuria: relationship between serum phenylalanine levels and ADC values in cerebral white matter.

PURPOSE: To prospectively determine the relationship between serum phenylalanine levels and apparent diffusion coefficient (ADC) values in the cerebral white matter of patients with phenylketonuria (PKU). MATERIALS AND METHODS: Institutional review board approval was obtained, and participants provided informed consent. Magnetic resonance (MR) imaging, which included T1- and T2-weighted, fluid-attenuated inversion-recovery (FLAIR), and diffusion-weighted examinations, was performed in 21 patients with PKU (nine male and 12 female patients; age range, 3-44 years; mean age, 19.4 years). ADC values in deep cerebral white matter were calculated for each patient. Serum phenylalanine levels were obtained in all patients within 12 days after MR imaging. Serum phenylalanine levels were measured in 16 patients 1 year before MR imaging. ADC values in cerebral white matter and serum phenylalanine levels were compared. A total of 21 control subjects (12 male and nine female patients; age range, 3-33 years; mean age, 20.6 years) underwent MR imaging. ADC values in cerebral white matter were compared with serum phenylalanine levels by using the Pearson correlation. RESULTS: Abnormal high signal intensity in white matter on T2-weighted and FLAIR MR images was noted in patients with PKU who had serum phenylalanine levels of more than 8.5 mg/dL (514.2 micromol/L). Diffusion in posterior deep cerebral white matter tended to be restricted in patients when increased serum phenylalanine levels were measured after MR imaging (r = -0.62). There was a correlation between ADC values in posterior cerebral white matter and serum phenylalanine levels measured 1 year before MR imaging (r = -0.77). ADCs of control subjects were significantly higher than ADCs of patients with PKU (P < .005). CONCLUSION: Posterior deep white matter in patients with PKU and a serum phenylalanine level of more than 8.5 mg/dL showed high signal intensity in white matter on T2-weighted and FLAIR MR images and revealed decreased ADC. We suggest that to avoid brain-restricted diffusion due to hyperphenylalanemia, patients with PKU should maintain serum phenylalanine levels of less than 8.5 mg/dL (514.2 micromol/L).

Evaluation of 18F-FDG PET with bladder irrigation in patients with uterine and ovarian tumors.

UNLABELLED: The purpose of this study was to evaluate PET using (18)F-FDG for gynecologic lesions with continuous bladder irrigation to eliminate artifacts from the (18)F-FDG activity in the bladder. METHODS: Forty-one patients were studied. They had 23 cervical uterine lesions (15 cases of cancer, 5 recurrences, 3 nonrecurrences); 8 cases of uterine corpus cancer, including 2 recurrences; and 10 ovarian masses (6 malignant, 4 nonmalignant). All cases of cancer were histologically proven; however, 2 cases of nonrecurrent uterine cervical carcinomas were diagnosed by clinical course. Continuous bladder irrigation was performed 35-55 min after intravenous administration of 185-370 MBq (18)F-FDG, and an emission scan was obtained 40-55 min after intravenous administration. Standardized uptake value (SUV) was used to estimate the degree of (18)F-FDG uptake quantitatively. RESULTS: After bladder irrigation, the (18)F-FDG activity in the urinary tract was eliminated in 33 patients, so that detection of tumor (18)F-FDG accumulation was easy. Two patients showed residual activity in the urinary bladder, and 6 patients showed activity in the ureter. An artifact was seen in 1 patient with residual activity in the urinary bladder caused by insufficient irrigation. However, these residual activities had no influence on detecting (18)F-FDG accumulation in tumor. The mean (+/-SD) of SUVs of malignant lesions was 6.04 +/- 3.22, that of nonmalignant lesions was 1.71 +/- 1.12, and the difference was significant (P = 0.0002). SUVs of all malignant lesions were greater than 2.0, and SUVs of all nonmalignant lesions, except the 1 case of ovarian fibroma, were less than 2.0. CONCLUSION: (18)F-FDG PET with continuous bladder irrigation is useful for eliminating (18)F-FDG activity in the bladder and for differentiating between malignant and nonmalignant uterine or ovarian masses.

The usefulness of 18F-FDG PET images obtained 2 hours after intravenous injection in liver tumor.

UNLABELLED: Liver tumors, especially hepatocellular carcinomas (HCCs), often exhibit no contrast with surrounding non-tumorous liver tissue in F-18-fluoro-2-deoxy-2-fluoro-D-glucose (FDG) positron emission tomography (PET) images obtained at the usual interval of one hour after intravenous FDG injection. We evaluated the usefulness of FDG PET studies of liver tumors performed 2 hours after intravenous injection. METHODS AND MATERIALS: Fifteen pretherapeutic patients with 33 liver tumors were studied, including 11 patients with 18 HCCs, and 4 patients with 15 metastatic liver tumors (METAs) from 3 colorectal carcinomas and 1 esophageal carcinoma. After transmission scans, emission scans were obtained 45-55 minutes and 115-125 minutes after intravenous injection of 185-370 MBq FDG as early images and delayed FDG PET images, respectively. Visual analysis of early and delayed images was performed, and the FDG uptake in the tumor to that in nontumorous liver ratio (T/N ratio), the FDG uptake in tumor to that in soft-tissue ratio (T/S ratio) and the FDG uptake in non-tumorous liver to that in soft-tissue ratio (N/S ratio) were calculated for each image. RESULTS: In visual analysis, visual improvement seen in images was observed in 6 of 18 HCC lesions and all 15 META lesions. In quantitative analysis, the mean T/S ratio and T/N ratio of HCCs in early images were 4.97 and 1.90, respectively, and those in delayed images were 6.24 and 2.20, respectively. The mean T/S ratio and T/N ratio of METAs in early images were 5.97 and 2.21, respectively, and those in delayed images were 6.99 and 3.80, respectively. The T/S ratio of HCCs and T/S ratio and T/N ratio of METAs were significantly higher in delayed images than in early images. The mean N/S ratios of HCC cases were 2.58 in the early images and 2.57 in the delayed images, but the ratio showed no constant tendency in the images. All N/S ratios of META cases were decreased in delayed images, although the significance of the difference between early and delayed images in N/S ratios was not analyzed because of the small number of cases. CONCLUSION: FDG PET studies performed 2 hours after intravenous injection were useful for clear visualization of liver tumors, especially metastatic liver tumors.