BACKGROUND & AIMS
Augmenter of liver regeneration (ALR, encoded by GFER) is a widely distributed pleiotropic protein originally identified as a hepatic growth factor. However, little is known about its roles in hepatic physiology and pathology. We created mice with liver-specific deletion of ALR to study its function.
METHODS
We developed mice with liver-specific deletion of ALR (ALR-L-KO) using the albumin-Cre/LoxP system. Liver tissues were collected from ALR-L-KO mice and ALRfloxed/floxed mice (controls) and analyzed by histology, reverse-transcription PCR, immunohistochemistry, electron microscopy, and techniques to measure fibrosis and lipids. Liver tissues from patients with and without advanced liver disease were determined by immunoblot analysis.
RESULTS
Two weeks after birth, livers of ALR-L-KO mice contained low levels of ALR and ATP; they had reduced mitochondrial respiratory function and increased oxidative stress, compared with livers from control mice, and had excessive steatosis, and hepatocyte apoptosis. Levels of carbamyl-palmitoyl transferase 1a and ATP synthase subunit ATP5G1 were reduced in livers of ALR-L-KO mice, indicating defects in mitochondrial fatty acid transport and ATP synthesis. Electron microscopy showed mitochondrial swelling with abnormalities in shapes and numbers of cristae. From weeks 2–4 after birth, levels of steatosis and apoptosis decreased in ALR-L-KO mice, whereas numbers of ALR-expressing cells increased, along with ATP levels. However, at weeks 4–8 after birth, livers became inflamed, with hepatocellular necrosis, ductular proliferation, and fibrosis; hepatocellular carcinoma developed by 1 year after birth in nearly 60% of the mice. Hepatic levels of ALR were also low in ob/ob mice and alcohol-fed mice with liver steatosis, compared with controls. Levels of ALR were lower in liver tissues from patients with advanced alcoholic liver disease and nonalcoholic steatohepatitis than in control liver tissues.
CONCLUSIONS
We developed mice with liver-specific deletion of ALR, and showed that it is required for mitochondrial function and lipid homeostasis in the liver. ALR-L-KO mice provide a useful model for investigating the pathogenesis of steatohepatitis and its complications.
The purpose of this study was to determine the accuracy of radiographic and magnetic resonance imaging techniques in preoperative sizing for allograft meniscus transplantation. Twelve cadaveric knee specimens underwent sequential radiographs, magnetic resonance imaging scans, and arthrotomy. Meniscus dimensions were measured in multiple planes for the purpose of determining accuracy of imaging studies in comparison with actual meniscus dimensions. Overall, magnetic resonance imaging proved only slightly more accurate than conventional radiography. The mean difference between magnetic resonance imaging measurements and actual meniscus dimensions was 2.25 +/- 2.04 mm. The mean difference between radiographic measurements and actual meniscus dimensions was 2.35 +/- 1.79 mm. Neither imaging technique was accurate for measuring individual meniscus dimensions, with only 35% of images measuring within 2 mm of actual meniscus dimensions. Using less stringent criteria for accuracy (within 5 mm), radiography and magnetic resonance imaging were 79% and 83% reliable, respectively. Failure to obtain true anteroposterior or lateral images (15 degrees of external and internal rotation) increased measurement inaccuracy. Intraobserver agreement was significantly higher for magnetic resonance imaging than for radiography. Further research into the development of alternative techniques for more reliable meniscus sizing and better understanding of the tolerance for meniscus size mismatch is necessary.
The acromioclavicular (AC) joint may be affected by a number of pathologic processes, most commonly osteoarthritis, posttraumatic arthritis, and distal clavicle osteolysis. The correct diagnosis of a problem can usually be deduced from a thorough history, physical examination, and radiologic evaluation. Asymptomatic AC joint degeneration is frequent and does not always correlate with the presence of symptoms. Selective lidocaine injection enhances diagnostic accuracy and may correlate with surgical outcome. Nonoperative treatment is helpful for most patients, although those with osteolysis may have to modify their activities. In appropriately selected patients, open or arthroscopic distal clavicle resection is necessary to relieve symptoms. Recent biomechanical and clinical data emphasize the importance of capsular preservation and minimization of bone resection; however, the optimal amount of distal clavicle resection remains elusive. Patients with AC joint instability have poor results after distal clavicle resection.
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