Nonalcoholic steatohepatitis/nonalcoholic fatty liver disease is considered to be a hepatic manifestation of various metabolic disorders. However, its precise pathogenic mechanism is obscure. Oxidative stress and consequent lipid peroxidation seem to play a pivotal role in disease progression. In this study, we analyzed the localization of oxidized phosphatidylcholine (oxPC), a lipid peroxide that serves as a ligand for scavenger receptors, in livers of patients with this steatotic disorder. Specimens of nonalcoholic fatty liver disease (15 autopsy livers with simple steatosis and 32 biopsy livers with steatohepatitis) were examined via immunohistochemistry and immunoelectron microscopy using a specific antibody against oxPC. In addition, scavenger receptor expression, hepatocyte apoptosis, iron deposition, and inflammatory cell infiltration in the diseased livers were also assessed. Oxidized phosphatidylcholine was mainly localized to steatotic hepatocytes and some macrophages/Kupffer cells. A few degenerative or apoptotic hepatocytes were also positive for oxPC. Immunoelectron microscopy showed oxPC localized to cytoplasmic/intracytoplasmic membranes including lipid droplets. Steatotic livers showed enhanced expression of scavenger receptors. The number of oxPC cells was correlated with disease severity and the number of myeloperoxidasepositive neutrophils, but not with the degree of iron deposition. In conclusion, distinct localization of oxPC in liver tissues suggest that neutrophil myeloperoxidase-derived oxidative stress may be crucial in the formation of oxPC and the progression of steatotic liver disease. (HEPATOLOGY 2006;43:506-514.)

No abstract

Background/Aims: The aim of this study was to determine whether expression of P-glycoprotein (P-gp), multidrug-resistance-related protein 1 (MRP1), and lung resistance protein (LRP) was related to the response to induction chemotherapy and prognosis in untreated diffuse large B-cell lymphoma (DLBCL). Methods: We assessed immunohistochemical expression of P-gp, MRP1 and LRP, using formalin-fixed and paraffin-embedded specimens of lymph node in 41 patients with DLBCL. Association between expression of these three proteins and their impact on clinical outcome and prognosis was statistically evaluated. Results: P-gp was positive in 37% of subjects, MRP1 in 63%, and LRP in 68%. The complete remission rates achieved in the group expressing these multidrug resistance (MDR) proteins was significantly lower than in the group not expressing them (20 versus 58%; p = 0.025 in P-gp, 23 versus 80%; p < 0.001 in MRP1 and 32 versus 69%, p = 0.043 in LRP, respectively). Furthermore, the patients expressing LRP had a shorter overall survival rate than those that did not (median of 26 months versus median not reached; p = 0.013). Conclusions: These findings suggest that the three MDR proteins are important predictive factors for the clinical outcome and prognosis in patients with DLBCL.

These findings indicated that LYVE-1 attenuation in sinusoidal endothelium was one of the manifestations of capillarization, and was associated with hepatic disease progression.

Although many studies have revealed the association between cyclooxygenase-2 (COX-2) and carcinogenesis, the association between COX-2 and Hodgkin's lymphoma (HL) remains unknown. We examined the immunohistochemical expression of COX-2, p53, bcl-2, and Ki-67 in 33 patients with HL, and counted microvessels stained with CD34. Hodgkin and Reed - Sternberg (HRS) cells with COX-2 expression were scored as 0 = no staining; 1 = <25% of cells staining; 2 = 25-49%; 3 = 50-75%; and 4 = > or =75%. COX-2 expression was observed in 15 cases of classical HL. Nevertheless, neither accumulation of p53 nor bcl-2 expression was associated with COX-2 expression. The percentage of Ki-67 positive-HRS cells and microvessel density in COX-2 score groups 2-4 were significantly higher than those in score group 0, respectively. We show that COX-2 expression is associated with cell proliferation and angiogenesis in HL. These findings suggest that COX-2 may be a target for therapy in HL.