Peroxisome proliferator-activated receptor-γ in capillary endothelia promotes fatty acid uptake by heart during long-term fasting.

BACKGROUND: Endothelium is a crucial blood-tissue interface controlling energy supply according to organ needs. We investigated whether peroxisome proliferator-activated receptor-γ (PPARγ) induces expression of fatty acid-binding protein 4 (FABP4) and fatty acid translocase (FAT)/CD36 in capillary endothelial cells (ECs) to promote FA transport into the heart. METHODS AND RESULTS: Expression of FABP4 and CD36 was induced by the PPARγ agonist pioglitazone in human cardiac microvessel ECs (HCMECs), but not in human umbilical vein ECs. Real-time PCR and immunohistochemistry of the heart tissue of control (Pparg(fl/null)) mice showed an increase in expression of FABP4 and CD36 in capillary ECs by either pioglitazone treatment or 48 hours of fasting, and these effects were not found in mice deficient in endothelial PPARγ (Pparg(▵)(EC)(/null)). Luciferase reporter constructs of the Fabp4 and CD36 promoters were markedly activated by pioglitazone in HCMECs through canonical PPAR-responsive elements. Activation of PPARγ facilitated FA uptake by HCMECs, which was partially inhibited by knockdown of either FABP4 or CD36. Uptake of an FA analogue, (125)I-BMIPP, was significantly reduced in heart, red skeletal muscle, and adipose tissue in Pparg(▵)(EC)(/null) mice as compared with Pparg(fl/null) mice after olive oil loading, whereas those values were comparable between Pparg(fl/null) and Pparg(▵)(EC)(/null) null mice on standard chow and a high-fat diet. Furthermore, Pparg(▵)(EC)(/null) mice displayed slower triglyceride clearance after olive oil loading. CONCLUSIONS: These findings identified a novel role for capillary endothelial PPARγ as a regulator of FA handing in FA-metabolizing organs including the heart in the postprandial state after long-term fasting.

Hypertensive crisis due to contrast-enhanced computed tomography in a patient with malignant pheochromocytoma.

A 63-year-old man underwent computed tomography (CT) using intravenous low-osmolar iodine contrast medium (LOCM) 6 days after undergoing high-dose (131)I-MIBG therapy for metastatic pheochromocytoma. Immediately after the CT examination, his blood pressure increased to 260/160 mmHg (from 179/101 mmHg before the examination). Phentolamine mesilate was administered, and the blood pressure rapidly went back to normal. Although hypertensive crisis after administration of LOCM is rare, this case suggests that high-dose (131)IMIBG therapy may be a risk factor for hypertensive crisis after administration of intravenous LOCM.

Improvement of image resolution of brain SPECT by use of the wide-angle offset acquisition method.

OBJECTIVE: Cerebral SPECT images require high spatial and contrast resolution for precise evaluation of the abnormal tracer distribution in the brain. A shorter data acquisition time is preferable so that artifacts due to patient movement are avoided. We tried to shorten data acquisition time applying larger sampling angle and offset acquisition method, in which half degree of the step angle was shifted in the opposite gamma camera of the dual-detector SPECT system. METHODS: A simulation study was performed with a 3-dimensional mathematical phantom. The phantom studies were performed with a hot-rod phantom and a brain phantom. A clinical study with 99(m)Tc-ECD SPECT was also performed on a patient who had a cerebral infarction. Reconstruction of images was done for the normal 6° and 12° onset and 12° offset. Data for the 12° offset were acquired by shifting of sampling angles of the opposite detector by half (6°) of the sampling angles of 12°. The MLEM algorithm was used for image reconstruction. Image qualities in the simulation study, the phantom studies, and the clinical study were compared for the 6° and 12° onset, and for the 12° offset by quantitative analysis with use of profile curves. RESULTS: Analysis of the profile curves revealed that the image quality of the 12° offset was better than that of the 12° onset and compared to that of the 6° onset in the simulation study, the phantom studies, and the clinical study. CONCLUSIONS: The present study indicates that wide-angle offset data acquisition improves the image resolution of brain SPECT compared to onset data acquisition with the same sampling time.

Essential pre-treatment imaging examinations in patients with endoscopically-diagnosed early gastric cancer.

BACKGROUND: There have been no reports discussing which imaging procedures are truly necessary before treatment of endoscopically-diagnosed early gastric cancer (eEGC). The aim of this pilot study was to show which imaging examinations are essential to select indicated treatment or appropriate strategy in patients with eEGC. METHODS: In 140 consecutive patients (95 men, 45 women; age, 66.4 +/- 11.3 years [mean +/- standard deviation], range, 33-90) with eEGC which were diagnosed during two years, the pre-treatment results of ultrasonography (US) and contrast-enhanced computed tomography (CT) of the abdomen, barium enema (BE) and chest radiography (CR) were retrospectively reviewed. Useful findings that might affect indication or strategy were evaluated. RESULTS: US demonstrated useful findings in 13 of 140 patients (9.3%): biliary tract stones (n = 11) and other malignant tumors (n = 2). Only one useful finding was demonstrated on CT (pancreatic intraductal papillary mucinous tumor) but not on US (0.7%; 95% confidential interval [CI], 2.1%). BE demonstrated colorectal carcinomas in six patients and polyps in 10 patients, altering treatment strategy (11.4%; 95%CI, 6.1-16.7%). Of these, only two colorectal carcinomas were detected on CT. CR showed three relevant findings (2.1%): pulmonary carcinoma (n = 1) and cardiomegaly (n = 2). Seventy-nine patients (56%) were treated surgically and 56 patients were treated by endoscopic intervention. The remaining five patients received no treatment due to various reasons. CONCLUSIONS: US, BE and CR may be essential as pre-treatment imaging examinations because they occasionally detect findings which affect treatment indication and strategy, although abdominal contrast-enhanced CT rarely provide additional information.

Air embolism detected during computed tomography fluoroscopically guided transthoracic needle biopsy.

Air embolism is a rare but potentially fatal complication of percutaneous needle biopsy of the lung. We report a case of cerebral air embolism which occurred during computed tomography (CT)-guided needle biopsy. Air entering the aorta is depicted on CT-fluoroscopy images of the procedure.

A phase I radioimmunolocalization trial of humanized monoclonal antibody huA33 in patients with gastric carcinoma.

In order to determine the in vivo characteristics of huA33, an open label dose escalation biopsy-based phase I clinical trial and radioimmunolocalization study were conducted with a complement determinant region-grafted humanized monoclonal antibody against the A33 antigen in patients with gastric carcinoma. Thirteen patients were entered onto one of four dose levels (1.0, 2.0, 5.0 or 10.0 mg/m(2)). Patients with locally advanced (UICC-TNM [International Union Against Cancer-tumor, node, metastasis] stage over 2 but resectable at clinical diagnosis) gastric carcinoma received a single infusion of (131)I-huA33 1 week prior to surgery. Adverse events were monitored, and imaging studies with gamma camera plus ex vivo scintigraphy of the resected specimen, biodistribution study by dosimetry analysis of the biopsied and resected tissues, and immunohistochemical analysis were carried out and evaluated. No dose-limiting toxicity was observed during the trial. Therefore, the maximum tolerated dose was not reached. Although cancer tissues with + intensity and <25% extent by immunostaining in biopsied frozen sections did not show positive imaging or postoperative dosimetry findings, cancers with ++ or +++ intensity or wide (>25%) extent by frozen and paraffin sections in the biopsied specimen showed positive ex vivo tumor images and positive antigen expression in resected gastric cancer specimens, and the biodistribution analysis showed tumor uptake of (131)I-huA33. In conclusion, humanized monoclonal antibody huA33 demonstrated selective localization to gastric cancer that expressed A33 antigen strongly. These excellent targeting characteristics of huA33 indicate potential for targeted therapy of advanced gastric cancer that is refractory to cytotoxic therapy, and could also be exploitable for curatively resected early gastric cancer in an adjuvant setting.

Brain microhemorrhages detected on T2*-weighted gradient-echo MR images.

BACKGROUND AND PURPOSE: Multifocal microhemorrhages have been reported to be commonly found in the brain of patients with systemic hypertension and spontaneous brain hemorrhage. The factors associated with these lesions detected on T2*-weighted gradient-echo images were examined to determine whether these lesions serve to indicate different types of microangiopathy and to predict a patient's risk for symptomatic hemorrhage. METHODS: The study population consisted of 2164 patients who underwent 2416 consecutive brain MR imaging studies performed during 3 years. The patients with intracerebral hemorrhages due to vascular malformations, neoplasms, trauma, or intracranial surgery and those with incomplete medical records were excluded; 2019 cases were analyzed. RESULTS: The overall incidence of microhemorrhages was 9.8%, predominantly in the lentiform nucleus (n = 96), thalamus (n = 88), and cortical-subcortical region (n = 93). Presence of microhemorrhages had the highest significant correlation with history of hemorrhagic stroke (P <.0001); advancing age, hypertension, and prominent white matter hyperintensity on T2-weighted images had the next highest significant correlation. Cortical-subcortical microhemorrhages were more frequently observed in patients who had previous lobar hemorrhagic stroke (P <.005). Among 139 patients with microhemorrhages who could be clinically followed up for more than 1 month, four (2.9%) had new hemorrhagic stroke. CONCLUSION: The presence of microhemorrhages may be not only a direct marker of bleeding-prone small-vessel diseases but also an indicator of different types of microangiopathy and a predictor of further hemorrhagic stroke.