Evolution of living donor liver transplantation over 10 years: experience of a single center.

PURPOSE: To evaluate the changes in living donor liver transplantations (LDLTs) over the last 10 years, we analyzed our experience of performing LDLT in a single center. METHODS: We performed 73 LDLTs over the 10 years between 1997 and 2007 in Nagasaki University Hospital, Japan. RESULTS: Initially, from 1997 to 2003, LDLT was performed for pediatric patients; then, between 2004 and 2007, adult-to-adult LDLT was introduced, primarily for hepatocellular carcinoma (HCC) in liver cirrhosis. We also began performing LDLTs for adults with ABO-incompatible blood type combination in the latter period. As the number of adult-to-adult LDLTs increased, left-sided grafts became fi rst choice for these patients. Survival rates were 88.3%, 77.2%, 70.2% at 1, 3, and 5 years, respectively. There was a relatively low incidence of arterial complications, and although the incidence of biliary complications was high initially, it decreased with experience. Likewise, the operative time, blood loss, and hospital stay after LDLT also improved remarkably. CONCLUSION: Over the last 10 years the indications for, and operative techniques used in LDLT have changed dramatically, even in a single center in Japan

Alleviation of lipopolysaccharide/d-galactosamine-induced liver injury in leukocyte cell-derived chemotaxin 2 deficient mice

Leukocyte cell-derived chemotaxin 2 (LECT2) is a secreted pleiotropic protein that is mainly produced by the liver. We have previously shown that LECT2 plays an important role in the pathogenesis of inflammatory liver diseases. Lipopolysaccharide/d-galactosamine (LPS/d-GalN)-induced acute liver injury is a known animal model of fulminant hepatic failure. Here we found that this hepatic injury was alleviated in LECT2-deficient mice. The levels of TNF-α and IFN-γ, which mediate this hepatitis, had significantly decreased in these mice, with the decrease in IFN-γ production notably greater than that in TNF-α. We therefore analyzed IFN-γ-producing cells in liver mononuclear cells. Flow cytometric analysis showed significantly reduced IFN-γ production in hepatic NK and NKT cells in LECT2-deficient mice compared with in wild-type mice. We also demonstrated a decrease in IFN-γ production in LECT2-deficient mice after systemic administration of recombinant IL-12, which is known to induce IFN-γ in NK and NKT cells. These results indicate that a decrease of IFN-γ production in NK and NKT cells was involved in the alleviation of LPS/d-GalN-induced liver injury in LECT2-deficient mice

Iron-depletion promotes mitophagy to maintain mitochondrial integrity in pathogenic yeast <i>Candida glabrata</i>

<p><i>Candida glabrata</i>, a haploid budding yeast, is the cause of severe systemic infections in immune-compromised hosts. The amount of free iron supplied to <i>C. glabrata</i> cells during systemic infections is severely limited by iron-chelating proteins such as transferrin. Thus, the iron-deficiency response in <i>C. glabrata</i> cells is thought to play important roles in their survival inside the host's body. In this study, we found that mitophagy was induced under iron-depleted conditions, and that the disruption of a gene homologous to <i>ATG32</i>, which is responsible for mitophagy in <i>Saccharomyces cerevisiae</i>, blocked mitophagy in <i>C. glabrata</i>. The mitophagic activity in <i>C. glabrata</i> cells was not detected on short-period exposure to nitrogen-starved conditions, which is a mitophagy-inducing condition used in <i>S. cerevisiae</i>. The mitophagy-deficient <i>atg32</i>Δ mutant of <i>C. glabrata</i> also exhibited decreased longevity under iron-deficient conditions. The mitochondrial membrane potential in <i>Cgatg32</i>Δ cells was significantly lower than that in wild-type cells under iron-depleted conditions. In a mouse model of disseminated infection, the <i>Cgatg32</i>Δ strain resulted in significantly decreased kidney and spleen fungal burdens compared with the wild-type strain. These results indicate that mitophagy in <i>C. glabrata</i> occurs in an iron-poor host tissue environment, and it may contribute to the longevity of cells, mitochondrial quality control, and pathogenesis.</p