Cloning of a cDNA encoding the rat placental glutathione S-transferase: overproduction of the mRNA in hepatocellular carcinomas

Rat hepatocellular carcinomas and normal liver have been screened for mRNA sequences which are more abundant in the carcinomas than in livers. The screen was done by differential colony hybridization of a cDNA library constructed from the mRNA of a primary tumor induced by diethylnitrosamine (DEN). One cDNA was isolated which hybridizes to a 900 nucleotide mRNA present in abundance in six chemically induced rat hepatomas (both primary and transplantable), but is not detectable in normal adult or fetal (17 day) liver. The nucleotide sequence of this cDNA is identical to that reported by Suguoka et al. for the placental isoenzyme of rat glutathione S-transferase (GST-P) (Nucleic Acids Res. 13:6049). A comparison of the GST-P amino acid sequence with those of two liver GST isoenzymes (Yal and Yc) shows only 26% overall homology; however, this homology is concentrated in three regions of 50%, 68.2% and 34.5%. Genomic blotting experiments show that the overproduction of GST-P mRNA in three Morris hepatomas is not due to amplification of genomic DNA sequences hybridizing with the GST-P cDNA. However, hybridizing sequences are contained on at least 72 kb of genomic DNA, suggesting great complexity of the rat GST-P locus.     

Hepatocarcinogenesis due to chronic liver cell injury in hepatitis B virus transgenic mice.

Fifty-nine transgenic mice from a lineage that overproduces the hepatitis B virus large envelope polypeptide and accumulates high intrahepatic concentrations of hepatitis B surface antigen were followed for evidence of liver disease throughout their 24-month life span. By 4 months of age all mice displayed biochemical and histological evidence of moderately severe chronic hepatitis which was followed sequentially by the development of regenerative nodules and oval cell hyperplasia (by 6 months), liver cell adenomas (by 8 months), and hepatocellular carcinomas (by 12 months of age). One hundred % of mice in this lineage developed hepatocellular carcinoma by 20 months of age, whereas no histopathological changes were observed in age- and sex-matched nontransgenic littermate controls over the same period of observation. These results indicate that overproduction of the hepatitis B virus large envelope polypeptide initiates a process characterized by liver cell injury, inflammation, and regenerative hyperplasia, which places large numbers of hepatocytes at risk for the development of transforming mutations, and inexorably progresses to hepatocellular carcinoma. We suggest that this is a general mechanism of hepatocarcinogenesis that may be operative in human hepatitis B virus infection and other necroinflammatory liver diseases as well.     

The diagnostic value of anaesthetic hip injection in differentiating between hip and spinal pain

Aim  This study aimed at investigating the diagnostic value of a local anaesthetic hip injection test to differentiate between hip and spinal pain in patients presenting with concurrent hip and spine pathology. Study design  Prospective clinical series. Materials and methods  Forty-eight consecutive patients with a diagnostic dilemma of concurrent pathology under the care of one spinal surgeon in one centre were evaluated. The hip injection test involved an intra-articular injection of 0.5% Bupivacaine under fluoroscopic control. Positive response was defined as significant (>70%) or complete relief of pain. A minimal relief (<30%) or no relief of pain was considered a negative response to the injection. Results  Thirty-seven patients reported a positive response to the injection. Of these, 33 (89%) underwent successful hip replacement with complete relief of symptoms. One patient had an unsuccessful hip replacement. Three patients with a positive response declined surgery. Eleven patients had a negative response to the test. Ten of them responded satisfactorily to treatment directed towards their spinal pathology and one patient had a successful hip replacement. The sensitivity of the test was 97% and specificity 91%. There was no complication to the injection in any patient. Conclusion  Local anaesthetic hip injection test is a safe and reliable diagnostic tool in identifying the source of pain in patients with combination of hip and spinal pathology.