Predictive role of anti-gp210 and anticentromere antibodies in long-term outcome of primary biliary cirrhosis

Because some of the autoreactive T-cell clones specific for human PDC-E2 cross-react to mimicry peptides having an EIExDK motif derived from nuclear antigens such as human gp210 and sp100, we studied the clinical significance of antinuclear antibodies (ANA) in primary biliary cirrhosis (PBC) patients registered to the National Hospital Organization Study Group for Liver Disease in Japan (NHOSLJ). We found that there are two different types of progression in PBC; one is a hepatic failure-type progression which is represented by positive anti-gp210 antibodies and the other is a portalhypertension-type progression which is represented by positive anticentromere antibodies. We discuss the predictive role of these ANA in the long-term outcome of PBC and the mechanisms by which two different PBC progression types occur based on molecular mimicry and aberrant expression of nuclear antigens.     

A case of synovial sarcoma in the perivertebral space of the neck: clinical presentation, radiological findings and histopathological description

We report a case of synovial sarcoma in the neck that was initially considered to be a benign soft-tissue tumour. The mass appeared to originate in the perivertebral space, extending to the spinal canal via the C3/4 and C4/5 neural foramina. The mass also encased the right vertebral artery and this suggested a malignant soft-tissue tumour.     

Diverticulitis Causing a High Serum Level of Carbohydrate Antigen 19-9: Report of a Case

We report herein a rare case of diverticulitis causing a high serum level of carbohydrate antigen (CA) 19-9. A 52-year-old man was admitted to our hospital with lower abdominal pain. Laboratory data showed evidence of inflammation and a high serum level of CA 19-9 (370 U/ml). Computed tomography demonstrated thickening of the wall of the sigmoid colon. He was diagnosed as having diverticulitis of the sigmoid colon and was treated with antibiotics. Although his symptoms improved, the presence of a malignancy such as colorectal cancer could not be completely ruled out because of the persistently high serum level of CA19-9. A laparotomy was performed and the sigmoid colon was found to be adherent to the bladder. Under a diagnosis of diverticulitis, a sigmoidectomy was performed. Pathological examination revealed diverticulitis of the sigmoid colon, but there was no evidence of malignancy in the resected specimen. The serum CA19-9 level decreased to normal postoperatively and immunohistochemical staining revealed CA19-9 antigen in the cytoplasm of the diverticular epithelium. Therefore, a possible explanation for the high level of this tumor marker was diverticulitis of the sigmoid colon. Received: June 6, 2001 / Accepted: September 11, 2001     

Nitric oxide-mediated vasodilatory effect of atrial natriuretic peptide in forearm vessels of healthy humans

1. The aim of the present study was to determine whether the vasorelaxant effect of atrial natriuretic peptide (ANP) is, in part, endothelium dependent in humans. 2. We used veno-occlusive plethysmography to measure forearm blood flow (FBF) during intra-arterial infusions of ANP (4, 8, 16, 32 pmol/min per dL forearm tissue volume) before and after the inhibition of nitric oxide (NO) synthesis by N(G)-monomethyl-L-arginine (L-NMMA; 100 micromol) in seven normal healthy subjects. 3. Atrial natriuretic peptide caused a dose-dependent increase in FBF both before and after L-NMMA and significantly reduced the plasma concentration of angiotensin (Ang) II. Administration of L-NMMA significantly diminished the increase in FBF in response to ANP infusion (P < 0.05). 4. These results suggest that the forearm vasodilative response to ANP is modulated, in part, by an endothelium-derived NO-mediated mechanism associated with a decrease in AngII caused by ANP.     

Rapid bactericidal activities of carbapenems against Pseudomonas aeruginosa in simulating human plasma concentrations

The rapid bactericidal activities of panipenem (PAPM), imipenem (IPM), and meropenem (MEPM) against Pseudomonas aeruginosa were investigated by using in vitro pharmacodynamic model simulating the human plasma concentrations after intravenous drip infusion at 500 mg for 0.5 hours. Against P. aeruginosa PAO1, PAPM and IPM showed rapider reduction in viable cell counts than MEPM at 0.5 hours after exposure. All drugs showed more than 3 log10 reduction in viable cell counts at 2 hours after exposure and bacterial regrowth was not observed throughout 6 hours. The initial bactericidal activities of the drugs against 4 clinical isolates within 1 hour after exposure were also investigated by the same method. Against P. aeruginosa strain 12,475, the 3 drugs showed similar initial bactericidal activity but PAPM and IPM showed stronger initial bactericidal activity than MEPM against the other strains as did against P. aeruginosa PAO1. The morphological change of a strain 12,489, for which the initial bactericidal activities were different largely, after 0.5 hours exposure to simulated drug-concentrations was investigated by scanning electron microscope. PAPM and IPM induced morphological changes in most of the cells and cell lysis and bulge formation. On the other hand, MEPM induced changes of the surface structure of cells and slightly elongated cells, but not cell lysis.     

Dimerumic acid as an antioxidant from the mold, Monascus anka: the inhibition mechanisms against lipid peroxidation and hemeprotein-mediated oxidation

This study aimed to investigate the antioxidant mechanism of dimerumic acid isolated as the active component with a radical scavenging action from the mold Monascus anka, traditionally used for the fermentation of foods. Dimerumic acid inhibited NADPH- and iron(II)-dependent lipid peroxidation (LPO) of rat liver microsomes at 20 and 200 microM, respectively. When ferrylmyoglobin was incubated with dimerumic acid, the myoglobin was scavenged and an electron spin resonance (ESR) signal with nine peaks was observed. The spin adduct was identified as a nitroxide radical by analysis of hyperfine structure. Similar ESR signal was also detected by incubation of dimerumic acid with peroxyl radicals. Thus, it was clarified that the antioxidant action of dimerumic acid is due to one electron donation of the hydroxamic acid group in the dimerumic acid molecule toward oxidants resulting in formation of nitroxide radical.     

2a-[4-(Tetrahydropyridoindol-2-yl)butyl]tetrahydrobenzindole derivatives: new selective antagonists of the 5-hydroxytryptamine7 receptor

A series of tetrahydrobenzindoles was prepared, and the affinity of these compounds for the 5-hydroxytryptamine7 (5-HT7) receptor and other receptors was evaluated. Most of the compounds showed high affinity for the 5-HT7 receptor, and 2a-[4-(tetrahydropyridoindol-2-yl)butyl]tetrahydrobenzindole derivatives (26a-j) exhibited high selectivity for this receptor. The nature of the substituent at the 9-position of the tetrahydropyridindole ring affected the affinity for the 5-HT7 receptor, and the 9-carbamoyl moiety afforded increased selectivity. Compound 26j exhibited high affinity for the 5-HT7 receptor, with at least 280-fold selectivity over the 5-HT2 receptor. In a functional model of 5-HT7 receptor activation, this compound was confirmed to have 5-HT7 receptor antagonist activity. It should be a useful tool for clarifying the biological role of the 5-HT7 receptor.     

Antineoplastic agents. 489. Isolation and structures of meliastatins 1-5 and related euphane triterpenes from the tree Melia dubia

The bark of the giant neem tree Melia dubia was found to contain 11 euphane-type triterpenes. Five new compounds, meliastatins 1-5 (1-5), proved to inhibit growth of the P388 lymphocytic leukemia cell line (ED(50) 1.7-5.6 microg/mL). Four of the others, the previously known methyl kulonate (8), kulinone (9), 16-hydroxybutyrospermol (10), and kulactone (11), were also found to inhibit (ED(50) 2.5-6.2 microg/mL) the P388 cancer cell line. In addition, two new euphane triterpenes were isolated and named dubione A (6) and dubione B (7). Structures for each of the 11 euphane triterpenes were established by spectral techniques that included HRMS and 2D NMR.