[Case of lymphangioleiomyomatosis associated with protein-losing gastroenteropathy].

A 29-year-old woman was referred to our hospital for the intensive examination of leg edema and hypoproteinemia. CT scan of showed multiple thin-walled cysts in both lungs, suggesting lymphangioleiomyomatosis. CT scan of the abdomen, lymphoscintigraphy showed enlarged abdominal lymph nodes. Protein loss from the gastrointestinal tract was documented by measurement of the clearance of alpha-1 antitrypsin from the plasma using a 72 h stool collection and (99m)Tc human serum albumin scintigraphy. We thought that secondary lymphangiectasia with lymphangioleiomyomatosis caused protein-losing gastroenteropathy. Dietary therapy resulted in symptomatic improvement.

Autoimmune hepatic inflammation by vaccination of mice with dendritic cells loaded with well-differentiated hepatocellular carcinoma cells and administration of interleukin-12.

Vaccination of mice with dendritic cells loaded with Hepa1-6, well-differentiated hepatocellular carcinoma cell line (DC/Hepa1-6), induced cytotoxic T lymphocytes against Hepa1-6. Liver-specific inflammation was generated by vaccination of mice with DC/Hepa1-6 and subsequent administration of interleukin (IL)-12. Vaccination with DCs loaded with MC38 or B16 and administration of IL-12 did not generate significant liver-specific inflammation. Splenic T cells from DC/Hepa1-6-vaccinated mice showed proliferative response by stimulation with S-100 protein of the liver and showed cytotoxic activity to hepatocytes. Hepatic mononuclear cells from DC/Hepa1-6 + IL-12-treated mice also showed cytotoxic activity to hepatocytes. Adoptive transfer of splenocytes from DC/Hepa1-6-vaccinated mice produced hepatic inflammation in recipient mice that had been pretreated with IL-12. IL-12 upregulated the expression of adhesion molecules and chemokines in the liver. In conclusion, CTLs responsive to hepatocytes induced by DC/Hepa1-6 and enhanced expression of adhesion molecules and chemokines in the liver by IL-12 would produce autoimmune hepatic inflammation.

[Significance of serum oxidative stress related markers and genotype of GST gene in the pathogeneses of primary biliary cirrhosis].

The studies using an immunohistological technique revealed that overexpression of oxidative stress-related substance such as HNE was observed in the liver of primary biliary cirrhosis patients. These data suggested that oxidative stress participated in the pathogenesis of primary biliary cirrhosis. Therefore we analyzed serum oxdative stress marker (8-OHdG) and anti oxidative substances (Mn-SOD and TRX) to evaluate their clinical significance. In addition we analyzed the genotype of anti oxidative substance GST that has been reported to relate susceptibility of autoimmune disease. Serum levels of 8-OHdG, Mn-SOD and TRX in PBC patients were significantly higher than those of healthy subjects (P<0.001). Though there was no relation between serum level of 8-OHdG and clinical data, positive correlation between serum level of Mn-SOD, TRX and serum level of ALP, IgM was observed. Positive correlation was also observed between serum level of Mn-SOD and TRX. Serum levels of Mn-SOD of patients who responded to UDCA therapy were significantly higher than those of patients who did not response to therapy (P<0.01). Although genotypic difference of GSTM1 and GSTT1 by peripheral blood mononuclear cells did not relate to susceptibility of PBC, serum titer of AMA of GSTM1 null and GSTT1 null patients were significantly higher than those of GSTM1 positive and/or GSTT1 positive patients (P< 0.05). These findings suggest that serum oxidative stress-related markers may reflect the extent of liver damage of PBC, and may relate to the efficacy of UDCA therapy on PBC. It also made clear that genotype of GST related to the titer of AMA.