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Although regioselective removal of 6-O-sulfate groups of heparin has been undertaken by several researchers, complete 6-O-desulfation with little side reaction has not been attained successfully. In this work, a modified method with a certain silylating reagent, N-methyl-N-(trimethylsilyl)trifluoroacetamide, has been established to produce completely 6-O-desulfated heparin with few other chemical changes. The degrees of 6-O-desulfation were estimated by means of chemical disaccharide analyses and/or 13 C NMR spectra. Although the completely 6-O-desulfated heparin lost about 20% of 2-O-sulfate groups, any other chemical changes and depolymerization were not detected. The completely 6-O-desulfated heparin displayed strong inhibition of COS-1 cell adhesion to basic fibroblast growth factor (bFGF)-coated well in a dose-dependent manner, as was clarified by the competitive cell-adhesion assay. Furthermore, the completely 6-O-desulfated heparin was shown to promote in vitro A31 fibroblast proliferation in a dose-dependent manner in the presence of bFGF. These results suggest that signal transduction through bFGF/bFGF receptor in A31 cells occurs in the absence of 6-O-sulfate groups in heparin. The involvement of 6-O-sulfate group(s) of heparin/heparan sulfate in the promotion of bFGF mitogenic activity was reported by several groups. This discrepancy between our results and those of other groups would be due to the differences in molecular size of heparin/heparan sulfate derivatives and/or cell species used for the assay. Heparin and heparan sulfate (HS)1 are known as glycosaminoglycan (GAG) components of extracellular matrix-forming connective tissues of animals. The former GAG, heparin, is exclusively distributed in mast cells, and the latter GAG, HS, is widely distributed in animal tissues. With the accumulation of the information concerning biological roles of heparin and HS, it has been revealed that their biological functions mostly depend upon interaction between polysaccharides and physiologically active molecules, although the biological roles of heparin and HS are highly diverged. For instance, they interact with lipoprotein lipase (1, 2), anti-thrombin III (3, 4), basic fibroblast growth factor (bFGF) (5-8), etc. Furthermore, minimum structures of heparin and/or HS necessary for binding with antithrombin III and/or bFGF have been determined (9, 12). Chemical modification of heparin has been undertaken by several researchers, focusing on the elucidation of the mechanism underlying interaction between heparin and the physiologically active molecules as described above. Specific removal of major sulfate groups of heparin such as 2-O-sulfate, 6-Osulfate, and N-sulfate groups would be useful in order to clarify the backbone structures of oligosaccharides bearing specific array of sulfate groups responsible for the interactions with physiologically active molecules. For instance, selective removal of 6-O-sulfate groups from glucosamine residues of heparin is of great importance in order to evaluate the involvemen...

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palliative operations such as marsupialization with biliary drainage, Patients with alveolar echinococcosis of the liverand laparotomy were performed in 14, 5, and 1 cases, respectively.(AEL) can be cured by complete excision of the lesions;Mebendazole had been given before albendazole therapy in 9 cases. however, it is not always completely resectable in ad-Eight patients had lung metastasis, and 2 had lymph node metastavanced cases. Recently, benzimidazole-type drugs have sis. The staging system proposed by Nakajima et al. 10 was used.been reported to be effective in nonresectable AEL. One Five groups (I, II, IIIa, IIIb, and IV) are obtained according to three hundred fifty-two patients with AEL have been surgi-principal degrees of anatomic extent: apparent localization of the cally treated in our institution since 1937. Our clinical site of origin (occupied segments); evidence of regional spread to the adjacent tissue or organ, usually in the form of direct invasion; and trial with albendazole, one of the benzimidazole carba- A IIIb indicates, in addition to involvement of one to three segments, favorable response to albendazole, such as decreases in regional tissue or organ invasion and/or distant metastasis, but all the size of the lesions, changes in cyst morphology, and lesions should be resectable. Stage IV indicates intrahepatic lesions amelioration in clinical symptoms or signs, was achieved occupied in four segments and/or regional invasion and/or distant in 11 (55%) cases. These favorable responses were also metastasis of which every lesion is nonresectable (i.e., curative operation cannot be achieved).10 Advanced stages were seen frequently; seen in cases of noncurative resection and palliative opthere were 1, 3, 4, 6, and 12 cases in stages I, II, IIIa, IIIb, and IV, eration. The cumulative survival rate of the patients was respectively. 87%, 15 years after the operation. A complete responseHematological examination and liver function tests were perwas achieved in one case; the residual lesion in the liver formed every 2 weeks, and serological tests and ultrasound (US) and completely disappeared on the computed tomography computed tomography (CT) scans were carried out at approximately image 3.5 years after noncurative surgery. Palliative or 6-month intervals. The drug protocol for albendazole (200-mg tablets; mass reduction surgery combined with albendazole obtained from SmithKline Beecham, Tokyo, Japan) was 10 mg/kg/d therapy may be a strategy for advanced disease, espe-orally in a treatment cycle of 4 weeks with 2-week breaks.3 This cycle cially when complete resection might result in signifi-was repeated indefinitely unless there were adverse reactions. The average duration of treatment was 3.25 years. cant morbidity or mortality. (HEPATOLOGY 1997;25:The study protocol of chemotherapy was approved by the ethics 528-531.)committee of the Department of Medicine of Hokkaido University. Chemotherapy was performed in patients after their informed conPatients with alveolar echinococcosis of the live...