Studies were conducted to develop a new DPPIV–/–/Rag2–/– mouse model for hepatocyte transplantation by allogeneic and xenogeneic cells and to compare the proliferative capacity of p27 null hepatocytes versus normal hepatocytes in this system. Dipeptidyl peptidase IV (DPPIV) gene knockout mice, in which wild-type (wt) DPPIV+ donor hepatocytes can be readily identified by enzyme histochemistry, were bred with Rag2 null mice to prepare immunotolerant DPPIV–/–/Rag2–/– double knockout mice. DPPIV–/–/Rag–/– mice were transplanted with wt hepatocytes or p27 null mouse hepatocytes, which show enhanced cell cycle activity due to disruption of the Kip1 cyclin kinase inhibitor gene, and liver repopulation was assessed under nonproliferative versus proliferative experimental conditions. After their initial engraftment, transplanted wt hepatocytes did not proliferate in untreated livers or increase significantly in response to an acute liver regenerative stimulus. p27 null hepatocytes engrafted with the same efficiency as wt hepatocytes, but showed a noticeable, although not statistically significant, increase in proliferation in response to partial hepatectomy or acute CCl4 administration. Repeated treatments with CCl4 substantially increased proliferation and liver repopulation by p27 null hepatocytes but not by wt hepatocytes. These results suggest that p27 gene inactivation does not overcome proliferative restrictions imposed on hepatocytes by the normal liver, but that after repeated episodes of toxic liver injury, the augmented proliferative capacity of p27 null hepatocytes leads to significant liver repopulation compared with wt hepatocytes. These properties of p27-deficient hepatocytes could prove useful as a target for liver repopulation in patients with intermittent or a low level of chronic liver injury.

Arginine treatment is able to reduces attacks of hyperammonemia in boys with late-onset OTCD and to increase their growth.

Key words focal nodular hyperplasia, glycogen phosphorylase, glycogen storage disease.Although it is well known that hepatic tumors often develop in patients with glycogen storage disease (GSD) types Ia and III, the formation of these tumors has not been reported in other forms of hepatic GSD. In this report, a patient with GSD type VI (phosphorylase deficiency; OMIM 232700) complicated with a hepatic benign tumor, focal nodular hyperplasia (FNH), is presented. This case indicates that regular check-ups for hepatic tumors are necessary, not only in patients with GSD types Ia or III, but also in patients with other forms of hepatic GSD. Case ReportA female patient was referred to our hospital when she was 5 years of age for further investigation of hepatomegaly, which had been detected when she had visited a clinic when she was 5 years old. She was born to healthy non-consanguineous parents and had no history of hypoglycemia or nasal bleeding. On physical examination, her height was 101 cm (-1.5 SD) and her bodyweight was 16 kg (-1.0 SD). The liver was firm and palpable 7 cm below the right costal margin, whereas the spleen was not palpable. The results of a fasting blood test collected at that time were as follows: aspartate aminotransferase 37U/L, alanine aminotransferase 24U/L, blood glucose 85 mg/dL, lactate 6.2 mg/ dL, uric acid 5.9 mg/dL, total cholesterol 229 mg/dL and triglyceride 88 mg/dL. A plain abdominal computed tomography (CT) scan showed an enlarged liver with a density considerably higher than that of the spleen (CT values: liver, 80; spleen, 42) ( Fig. 1). Glucose and galactose loading tests were performed. The serum lactate level was not elevated when glucose was loaded, although it increased to a maximum of 56 mg/dL one hour after loading (normal <35 mg/dL). A glucagon loading test was performed after a 15-h fast, with the serum glucose level increasing from 71 to 128 mg/dL one hour after loading. On the basis of these data, GSD was suspected and accordingly the enzyme activities of hepatic GSD, that is, debranching enzyme, phosphorylase and phosphorylase b kinase, were measured in peripheral blood. The results of all these tests were normal (Table 1). Informed consent for a liver needle biopsy for measurement of enzyme activity was not obtained. Although the enzyme activity of phosphorylase b kinase measured in peripheral blood was normal, a tentative diagnosis of GSD type IX (phosphorylase b kinase deficiency) was made based on the physical, laboratory and radiological findings and the results of the loading tests. Regular check-ups including abdominal CT scans for potential formation of hepatic tumor were performed every year. The patient's growth curve showed that she attained mean values around the time of puberty. The results of blood tests obtained between 5 and 14 years of age were as follows (mean 1 SD): uric acid 5.9 1 0.6 mg/dL, total cholesterol 208 1 21.0 mg/dL and triglyceride 198 1 111 mg/dL.When the patient was 15 years of age, the early phase of a contrast-enhanced abdominal CT ...

No abstract

Results and Conclusion: [ 14 C]MeAIB uptake occurred principally via a Na + -dependent A type mechanism whereas [ 3 H]MET uptake, which occurred predominantly via a Na + -independent L type mechanism although other transporters were also utilized depending on cell type. There was no correlation between [ 3 H]MET uptake and total system L amino acid transporter (LAT) expression. In contrast, [ 14 C]MeAIB uptake strongly correlated with total system A amino acid transporter (SNAT) expression and proliferative activity in this preliminary study using four human carcinoma cell lines. Carcinoma proliferative activity also correlated with total SNAT expression.