ABSTRACT
A 27-year-old man who had been diagnosed as having chronic hepatitis B suffered disease exacerbation with marked reactivation of hepatitis B virus (HBV). Treatment with interferon (IFN) did not improve his condition, and his serum HBV DNA level increased to over 10 000 pg/ml during IFN administration. Following replacement with lamivudine, there was a substantial reduction in HBV DNA to an undetectable level, and liver function parameters subsequently improved to within the normal range. Quantitative analysis of the precore mutant HBV DNA, which is a variant that cannot express hepatitis B e antigen due to a G-to-A point mutation in the precore region of the viral genome, revealed that the amount present was greater than for the precore wild-type HBV DNA in the serum taken before IFN treatment. This case suggests that lamivudine would be an appropriate alternative to IFN, particularly in patients infected with HBV containing an excess of precore mutants resistant to IFN therapy.
Subject(s)
Antiviral Agents/therapeutic use , Hepatitis B virus/genetics , Hepatitis B, Chronic/drug therapy , Hepatitis B, Chronic/virology , Lamivudine/therapeutic use , Adult , Amino Acid Motifs/genetics , Amino Acid Sequence , Base Sequence , DNA Primers/genetics , Drug Resistance , Hepatitis B Core Antigens/genetics , Hepatitis B virus/isolation & purification , Humans , Interferon-alpha/therapeutic use , Male , Point Mutation , Viremia/drug therapy , Viremia/virologyABSTRACT
BACKGROUND AND STUDY AIMS: The indications for laparoscopic microwave coagulation therapy (LMCT) for hepatocellular carcinoma (HCC) have not yet been adequately evaluated. This study investigated the value of LMCT in the treatment of HCC. PATIENTS AND METHODS: Forty-three patients with liver cirrhosis (including five patients in Child Pugh grade C), with 56 HCC lesions, were enrolled in the study. When dynamic computed tomography (CT) showed a loss in HCC enhancement characteristics and a low concentration area after LMCT, a lesion was judged to have undergone complete necrosis. RESULTS: The rate of complete necrosis for lesions measuring 40 mm or less was significantly higher (P<0.01) than for those measuring 41 mm or more. The rate of complete necrosis for lesions located on the liver surface, excluding those located close to the gallbladder or in contact with the diaphragm, was also significantly higher (P<0.01) than for those situated deep within the liver. The outcome for lesions of 40 mm or less was favorable. Intra-abdominal hemorrhage occurred in two patients, pneumothorax in three, and hepatic infarction in one, all associated with LMCT. However, these patients did not suffer any sequelae of clinical significance. CONCLUSIONS: This study suggests that there is a strong indication for LMCT for HCCs measuring 40 mm or less in diameter and those located on the liver surface even if they are as large as 50 mm, but not for those located close to the gallbladder or in contact with the diaphragm. LMCT appears to be applicable in patients with impaired liver function.
Subject(s)
Carcinoma, Hepatocellular/therapy , Hyperthermia, Induced/instrumentation , Laparoscopy , Liver Neoplasms/therapy , Aged , Aged, 80 and over , Carcinoma, Hepatocellular/pathology , Female , Humans , Liver/pathology , Liver Neoplasms/pathology , Male , Middle Aged , Necrosis , Treatment OutcomeABSTRACT
As the first non-peptide endothelin receptor antagonist from a higher plant, a new triterpenoid, myriceric acid A (50-235) (1) was isolated from the bayberry, Myrica cerifera. Myriceric acid A (1) inhibited not only an endothelin-1-induced increase in cytosolic free Ca2+ concentration (IC50 = 11 +/- 2 nM) but [125I]endothelin-1 binding in rat aortic smooth muscle cells (Ki = 66 +/- 15 nM). Two new related triterpenoids, myriceric acid C (6), and myriceric acid D (8), were also isolated. Furthermore, the chemical modification of these natural products led to the synthesis of sulfated derivatives (13, 14, 15) which showed 1.5 to 20 times higher affinity for endothelin receptors. The structure activity relationships of myriceric acids and their derivatives are discussed.
Subject(s)
Endothelin Receptor Antagonists , Plants, Medicinal/chemistry , Triterpenes/isolation & purification , Animals , Calcium/metabolism , Cells, Cultured , Cytosol/drug effects , Cytosol/metabolism , Magnetic Resonance Spectroscopy , Molecular Conformation , Muscle, Smooth, Vascular/cytology , Muscle, Smooth, Vascular/drug effects , Rats , Structure-Activity Relationship , Triterpenes/pharmacologyABSTRACT
A new phenazine antibiotic, DOB-41, was isolated from the culture broth of a Pseudomonas strain. The antibiotic obtained as yellow crystals showed UV maxima at 255 nm and 370 nm. A molecular formula, C19H18N2O6, was indicated by elemental analysis and mass spectrometry. The structure was elucidated by X-ray diffraction analysis. The antibiotic exhibited inhibitory activity against Gram-positive bacteria, and antitumor effect against leukemia P388 in mice.