ALBERT

Description: tRNAs are unique among various RNAs in that they shuttle between the nucleus and the cytoplasm, and their localization is regulated by nutrient conditions. Although nuclear export of tRNAs has been well documented, the import machinery is poorly understood. Here, we identified Ssa2p, a major cytoplasmic Hsp70 in Saccharomyces cerevisiae, as a tRNA-binding protein whose deletion compromises nuclear accumulation of tRNAs upon nutrient starvation. Ssa2p recognizes several structural features of tRNAs through its nucleotide-binding domain, but prefers loosely-folded tRNAs, suggesting that Ssa2p has a chaperone-like activity for RNAs. Ssa2p also binds Nup116, one of the yeast nucleoporins. Sis1p and Ydj1p, cytoplasmic co-chaperones for Ssa proteins, were also found to contribute to the tRNA import. These results unveil a novel function of the Ssa2p system as a tRNA carrier for nuclear import by a novel mode of substrate recognition. Such Ssa2p-mediated tRNA import likely contributes to quality control of cytosolic tRNAs.

Description: Abstract 5001 Background: Renal insufficiency is one of the main complications in myeloma patients. Various causes were reported to be responsible for renal damage. Through analysis of an autopsied cases we would show the diversity of the renal diseases in myeloma. Methods: We studied 41 autopsied myeloma cases from 1979 to 2008 at the National Center for Global Health and Medicine. The kidneys were evaluated by light microscopy using hematoxilin-eosin-stained sections, as well as Congo-red stain when amyloidosis was suspected. Results: There were 21 men and 20 women. Mean age at autopsy was 64.5 years old. The most common lesion was cast nephropathy (41.5%). The giant cell invasion was found in 35.3% of patients with cast nephropathy. Plasma cell tumor involvement was detected in 29.3% of all 41 autopsied cases. Fourteen per cent of cases had both cast nephropathy and plasma cell tumor involvement. In 75.6% of the patients, arteriosclerosis was found. In addition, 32% of the patients had the glomerular sclerosis which involved more than 20% of the glomerulus. Other findings include acute tubular necrosis (31.7%), AL-amyloidosis (19.5%), renal calcification (17.1%), bacterial and fungal infection (7.7%), micro thrombo-embolism (7.7%), mesangial proliferation (4.9%). At least one of above findings were detected in all cases and combined findings were detected in 65.9% cases. Conclusion: We evaluated the renal manifestations in 41 autopsied cases in detail. In all cases, at least one pathological finding was detected. Cast nephropathy was the most common renal manifestation. However, direct myeloma cell invasion was found in 29.3% and combined pathologic findings were common. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 5004 Background: Despite recent progress in treatment, multiple myeloma is still uncurable disease. The impact of modern therapy on the causes of death and pathological feature of end-stage myeloma is not fully understood. Methods: We studied autopsied cases with multiple myeloma between 1979 and 2009 at National Medical Center of Global Health and Medicine, Tokyo, Japan. We compared the clinicopathological feature of the autopsied cases in recent 10 years with the cases before 2000. Statistical analysis was performed using student's t-test and chi-square test. Results: There were 81 autopsied cases between 1979 and 2009. 31 cases were autopsied in recent 10 years and the older 50 cases were before 2000. Mean age at death was 59.2 and 65.1 years old, and the mean duration of illness was 46.1 and 31.9 months, respectively. Stem cell transplantation was performed in 13 (12 autologous, 1 allogeneic) of recent cases and 3 (2 autologous and 1 allogeneic) of older cases. In recent cases, five patients were treated with bortezomib, 2 were with thalidomide and 2 were with both. Extramedullary infiltration of myeloma cells were observed in both groups. The frequent sites of involvement were spleen, liver, kidney, lymph nodes, lung, pancreas, adrenal gland and perioneum. The infiltration in liver and lung was significantly frequent in the recent cases than in the older cases (58.1% vs. 28.0%, p=0.007, and 38.7% vs. 18%, p=0.039). Infection as a cause of death was noted more frequently in the recent cases than in the older cases (41.9% vs. 18.0%, p=0.019). Amyloid deposition was detected in 16.1% and 22.0% (ns.), and myeloma kidney was noted in 48.4% and 60% (ns.). Conclusion: High dose chemotherapy with stem cell support and novel agents have been contributed to improving the survival. However, the increase in resistant bacterial and fungal infection is serious problem. Also, extramedullary relapse after autologous and allogeneic stem cell transplantation is not rare, and extramedullary progression under thalidomide has been reported. In our recent autopsied cases, the incidence of fatal infection and extramedullary involvement of myeloma cells was significantly higher than in the older cases. Disclosures: No relevant conflicts of interest to declare.