Human midkine (hMK), a novel heparin-binding neurotrophic factor consisting of 121 amino acid residues with five intramolecular disulphide bonds, was synthesized by solution procedure in order to demonstrate the usefulness of our newly developed solvent system, a mixture of dichloromethane or chloroform and trifluoroethanol. The final protected 121-residue peptide was assembled from two large fully protected intermediates, Boc-(1-59)-OH and H-(60-121)-OBzl, in CHL/TFE(3:1, v/v) using water-soluble carbodiimide in the presence of HOOBt as coupling reagents. After removal of the protecting groups by HF followed by treatment with Hg(OAc)2 in 50% acetic acid, the fully deprotected peptide was subjected to the oxidative folding reaction. The final product was confirmed to have the correct disulphide structure from its tryptic peptide mapping and to possess the same biological activities as those of the natural product. In order to clarify the active region of the hMK molecule, the N-terminal half domains [(1-59) and (60-121)] were also synthesized by the same procedure used for the hMK synthesis. The C-half domain was confirmed to show the full pattern of bioactivities except for the neuronal cell survival activity, while the N-half one showed much less activity in general.

Amino Acid Sequence↗

PubMedDate not supplied

Hepatolithiasis associated with cholangiocarcinoma.

Hepatolithiasis is a risk factor for cholangiocarcinoma. It is difficult to make an accurate diagnosis before treatment. In a retrospective study, we identified characteristic clinical features of 103 patients with hepatolithiasis (group H) and 10 patients with hepatolithiasis associated with cholangiocarcinoma (group HC), and examined the methods for diagnosis and treatment. The main symptoms were abdominal pain, fever, and jaundice, although few patients in group HC had jaundice. The incidence of abnormal serum levels of carcinoembryonic antigen (CEA) in group HC was higher than in group H. The incidence of cholangiocarcinoma in cases in which most of the stones were present in the intrahepatic ducts of the left lobe (type I-L) was higher than the incidence in the other patients. Of the patients who underwent portography in group HC, portal veins in the portion of the liver containing the cholangiocarcinoma were not seen, and this region was atrophic in the operative specimens. The incidence of portal obstruction in portograms in group HC was higher than that in group H. The possibility of carcinoma should be kept in mind if there are high levels of CEA, if the location of the stones is classified as type I-L, or if portal veins cannot be seen on portograms. In such patients, liver resection should be considered because there may be undiagnosed cholangiocarcinoma.

Adolescent↗

PubMedDate not supplied

Extension of surgical indications for hepatocellular carcinoma by portal vein embolization.

We studied, clinically and experimentally, hypertrophy of the part of the liver not embolized after portal vein embolization (PVE). The subjects of the clinical study were 29 patients with hepatocellular carcinoma (HCC) who underwent embolization of the right first portal branch; 19 patients had cirrhosis, and 10 did not. The volume of the liver was calculated from computed tomograms obtained before PVE and 2 weeks after. In all patients, the volume of the nonembolized (left) lobe increased significantly. For the experimental study, we used male Wistar rats. Normal rats were untreated, and in the other rats cirrhosis was induced with carbon tetrachloride. The portal branch that supplies 70% of the total volume of the liver was embolized. The rats underwent one of four procedures: 70% PVE, 70% portal vein ligation, 70% hepatectomy, or laparotomy only. Rats wre killed at different times after surgery, and the livers were removed and weighed. The mitotic index and DNA synthesis were measured in the nonembolized lobe (PVE group), in the lobe not supplied by the ligated branch (ligation group), or in the remaining liver (hepatectomy group). The liver weight, mitotic index, and DNA synthesis were high in the PVE, ligation, and hepatectomy groups for both normal rats and rats with cirrhosis. PVE caused cell proliferation and hypertrophy in the nonembolized part of the liver in the normal rats and even in those with cirrhosis. We concluded that PVE can extend the surgical indications for patients with HCC and underlying cirrhosis.

Adult↗

PubMedDate not supplied

Results of treatment of patients with hepatocellular carcinoma with severe cirrhosis of the liver.

We retrospectively classified patients with hepatocellular carcinoma by the results of tests of 15-minute indocyanine green retention (ICGR15). Of the 201 patients with hepatocellular carcinoma admitted to our department in the past 6 years, 36 patients were assigned to group 1 (ICGR15 less than 10.0%), 81 patients to group 2 (ICGR15 = 10.1-20.0%), and 84 patients to group 3 (ICGR15 greater than or equal to 20.1%). Of the total 201 patients, 72% underwent liver resection (78% of group 1 patients, 80% of group 2 patients, and 62% of group 3 patients). We regarded the cirrhosis of the patients in group 3 as severe and studied their survival rate classified by the treatment used. Of these 84 patients, 52 patients were treated by liver resection, about half of whom were treated preoperatively by transcatheter arterial embolization (TAE). Another 9 patients were treated preoperatively by both TAE and portal vein embolization (PVE). At 2 years, and again at 3 years, the survival rate was significantly higher when TAE was used preoperatively than with resection alone. We think that the possibility of performing needed liver resection will be enlarged by preoperative PVE and that liver resection can be done more safely after use of PVE in some patients.

Adolescent↗

PubMedDate not supplied

Comparative immunohistochemical study of insulin-like growth factor II and insulin-like growth factor receptor type 1 in pediatric brain tumors.

Insulin-like growth factor (IGF)-II is an important growth factor in development of the central nervous system. The purpose of this study was to evaluate expression of IGF-II and IGF receptor type 1 (IGFR1) in various pediatric brain tumors. Immunohistochemistry for IGF-II and IGFR1 was performed on 15 choroid plexus papillomas (CPPs) including 1 atypical CPP, 2 choroid plexus carcinomas (CPCs), 5 anaplastic ependymomas, 7 nonanaplastic ependymomas (simply referred to as "ependymoma"), 5 medulloblastomas, 1 cerebral neuroblastoma, and 1 atypical teratoid/rhabdoid tumor (ATRT) along with 10 non-neoplastic choroid plexus and 3 non-neoplastic ependymal linings. All non-neoplastic choroid plexus, CPPs, CPCs, anaplastic ependymomas, ATRT, 71% of ependymomas, and 67% of non-neoplastic ependymal linings showed cytoplasmic positivity for IGF-II, whereas all medulloblastomas and the cerebral neuroblastoma were negative for IGF-II. In addition to cytoplasmic positivity for IGFR1, membranous positivity was observed in 73% of CPPs, both CPCs, the ATRT, 22% of non-neoplastic choroid plexus, 80% of anaplastic ependymomas, and 29% of ependymomas, but not in any medulloblastoma, cerebral neuroblastoma, or non-neoplastic ependymal lining. IGF-II and IGFR1 may play roles in the pathogeneses of CPP, CPC, anaplastic ependymoma, ependymoma, and ATRT. Immunohistochemical testing for IGF-II and IGFR1 may be useful in differentiating ATRT, CPC, and anaplastic ependymoma from medulloblastoma and cerebral neuroblastoma.

Adolescent↗

PubMedDate not supplied

Phosphodiesterase type III inhibitor enhances the protective effects of adenosine against ischemic hepatic injury in rats.

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3',5'-Cyclic-AMP Phosphodiesterases↗