Opiates such as morphine and codeine are mainly obtained by extraction from opium poppies. Fermentative opiate production in microbes has also been investigated, and complete biosynthesis of opiates from a simple carbon source has recently been accomplished in yeast. Here we demonstrate that Escherichia coli serves as an efficient, robust and flexible platform for total opiate synthesis. Thebaine, the most important raw material in opioid preparations, is produced by stepwise culture of four engineered strains at yields of 2.1 mg l−1 from glycerol, corresponding to a 300-fold increase from recently developed yeast systems. This improvement is presumably due to strong activity of enzymes related to thebaine synthesis from (R)-reticuline in E. coli. Furthermore, by adding two genes to the thebaine production system, we demonstrate the biosynthesis of hydrocodone, a clinically important opioid. Improvements in opiate production in this E. coli system represent a major step towards the development of alternative opiate production systems.

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The outcome in 3225 patients with hepatocellular carcinoma (HCC) was studied in groups with equivalent prognosis treated with resection, transcatheter arterial embolization (TAE), and percutaneous transhepatic ethanol injection (PEI). Significant factors for better clinical background included a tumor diameter of < or = 30 mm, tumor number < or = 3 and (clinical) Stage I. In patients with Stage I disease having tumors of < or = 30 mm and < or = 3 in number, survival afer resection and PEI did not differ, while survival after TAE was significantly worse. In those patients with Stage II disease, survival after PEI was significantly better than after resection or TAE. In patients with Stage I or II disease having tumors > or = 31 in size and < or = 3 number, survival after resection was significantly better than after TAE. In patients with Stage I disease having tumors of > or = 31 mm and > or = 4 in number, survival after resection was significantly better than after TAE. Our conclusions are as follows. Firstly, resection or PEI is recommended for patients with Stage I disease having < or = 3 tumors all < or = 30 mm in size. Secondly, PEI is recommended for patients with Stage II disease having < or = 3 tumors all < or = 30 mm in size. Thirdly, for patients with Stage I disease having tumors 31 mm or larger in size, whatever the number of tumors, resection should be selected rather than TAE.

Background Eosinophilic myocarditis is a rare clinical entity characterized by eosinophilia and myocardial inflammation with infiltrating eosinophils. The prognosis of patients with eosinophilic myocarditis is difficult to determine due the disease's rarity and varied causes; consequently, standard treatment has not been established.

Adult T-cell leukemia (ATL) develops in a human T-cell leukemia virus type I (HTLV-I) carrier. The development of malignancy during immunosuppressive treatment following organ transplantation is one of the late fatal complications. We describe the development of three cases of ATL in eight HTLV-I carriers within 164 living-donor liver transplant recipients undergoing immunosuppressive treatment. All three cases were immunosuppressed with tacrolimus. Acute-type ATL was diagnosed at 6, 9, and 25 months after living-donor liver transplantation, based on increased numbers of CD4+25+ lymphocytes exhibiting "flower-like" nuclei, and the elevation of lactate dehydrogenase. Southern blot analysis demonstrated the clonal proliferation of ATL cells in peripheral blood. The ATL cells originated from the recipient, as demonstrated by fluorescence in situ hybridization analysis using sex chromosomal markers. Our observations suggest that immunosuppressive treatment for the prevention of graft rejection after living-donor liver transplantation may induce the development of ATL in an HTLV-I carrier.