Alanine aminotransferase isoenzymes: molecular cloning and quantitative analysis of tissue expression in rats and serum elevation in liver toxicity.

UNLABELLED: The elevation of serum alanine aminotransferase (ALT) is regarded as an indicator of liver damage based on the presumption that ALT protein is specifically and abundantly expressed in the liver. However, ALT elevation is also observed in non-liver injury conditions (for example, muscle injury) and in apparently healthy people. Conversely, serum ALT activity is normal in many patients with confirmed liver diseases (for example, cirrhosis and hepatitis C infection). To improve the diagnostic value of the ALT assay and to understand the molecular basis for serum ALT changes in various pathophysiological conditions, we have cloned rat ALT isoenzyme ALT1 and ALT2 complementary DNAs (cDNAs), examined their tissue expressions at the messenger RNA and protein levels, and determined ALT1 and ALT 2 serum levels in response to liver damage in rodents. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis shows that ALT1 messenger RNA is widely distributed and mainly expressed in intestine, liver, fat tissues, colon, muscle, and heart, in the order of high to low expression level, whereas ALT2 gene expression is more restricted, mainly in liver, muscle, brain, and white adipose tissue. The tissue distribution pattern of ALT1 and ALT2 proteins largely agrees with their messenger RNA expression. Interestingly, hepatic ALT2 protein is approximately four times higher in male rats than in female rats. In addition, ALT isoenzymes distribute differentially at the subcellular level in that ALT1 is a cytoplasmic protein and ALT2 a mitochondrial protein, supporting bioinformatic prediction of mitochondrial localization of ALT2. CONCLUSION: Using animal models of hepatoxicity induced by carbon tetrachloride and acetaminophen, we found that both serum ALT1 and ALT2 protein levels were significantly elevated and correlated with ALT activity, providing, for the first time, the molecular basis for the elevated total serum ALT activity.

Adrenal phaeochromocytoma: correlation of MRI appearances with histology and function.

The purpose of this study was to describe the range of appearances of adrenal phaeochromocytomas on T2-weighted MRI, correlate appearances with histopathology, and quantify the incidence of the previously described hyperintense appearance. The appearance and MR characteristics of 44 phaeochromocytomas were reviewed retrospectively. T2-weighted appearances were grouped: (1) 'classical', homogeneous, high signal intensity, isointense to CSF; (2) homogeneous, isointense or minimally hyperintense to spleen, hypointense to CSF; (3) heterogeneous, marbled appearance; (4) heterogeneous, multiple high signal intensity pockets. All 44 adrenal phaeochromocytomas were well circumscribed, 1.2-15 cm in maximum diameter, with no visual or quantitative signal loss on chemical shift imaging. On T2-weighted MRI 5/44 (11%) had group 1 appearance; 15/44 (34%) group 2, 7/44 (16%) group 3; and 17/44 (39%) group 4. Homogeneous group 1 and 2 lesions were smaller (mean 4.5 cm) than heterogeneous group 3 and 4 lesions (mean 6.3 cm). Increasing MRI heterogeneity correlated pathologically with increasing amounts of haemorrhage, necrosis and fibrosis. No MRI features were predictive of malignancy. Non-functioning phaeochromocytomas were larger than functioning lesions. No size difference was seen between syndrome and sporadic lesions. In this large series we report a wide range of appearances of adrenal phaeochromocytomas on T2-weighted MRI. The previously described classical hyperintense phaeochromocytoma is relatively uncommon.