The antidepressants, imipramine and mianserin, have been reported to cause liver damage. We investigated a role of cytochrome P450 (CYP)-mediated formation of a reactive metabolite in antidepressant-induced acute cell injury using hepatocytes isolated from male and female Wistar rats, and male Dark Agouti rats, which have different relative abundance of CYP enzymes. Culture of the hepatocytes with imipramine and mianserin caused a marked decrease in glutathione followed by protein thiol, which preceded lactate dehydrogenase leakage. The decreases in glutathione and protein thiol contents by imipramine were significantly slower in hepatocytes from male Dark Agouti rats than those from male Wistar rats, whereas no significant sex difference in Wistar rats was observed. The decrease in thiol by mianserin was significantly slower in hepatocytes from female Wistar than those from male Wistar rats, whereas no significant differences were found between Wistar and Dark Agouti males. Results consistent with alteration of the thiols were obtained for lactate dehydrogenase leakage induced by imipramine and mianserin. These findings indicated that CYP-mediated metabolic activation was involved in acute cell injury induced by the antidepressants; namely a CYP2D enzyme(s), which is deficient in Dark Agouti rats, and a male specific CYP enzyme(s) were suggested to be responsible for the cytotoxicity of imipramine and mianserin, respectively.

Animals↗

PubMedDate not supplied

Myeloblastoma formation in acute myeloid leukemia.

The cell surface markers on the leukemic cells of 76 patients with adult acute myeloid leukemia (AML) have been analyzed by indirect immunofluorescence, and the presence of CD56+ leukemic cells was detected in ten of these patients. Four of these 10 CD56+ AML patients developed extramedullary myeloblastomas and in two of them an intracranial myeloblastoma. In contrast, in the remaining 66 CD56- AML patients, only one patient developed a myeloblastoma formation of the subcutaneous. It may be that the CD56 antigen which is an isoform of the neural cell adhesion molecule (NCAM), expressed on neurons, satellite cells of skeletal muscle cells, and on stromal cells, binds these tissues by a homophilic mechanism. CD56+ leukemic cells are capable of invading and of surviving in extramedullary tissues, where they proliferate and develop into a myeloblastoma. Because of this possibility, CD56+ AML patients should be carefully monitored for signs of myeloblastoma formation.

Adolescent↗

PubMedDate not supplied

Immunohistochemical localization of endothelin in human vascular endothelial cells.

The cellular localization of endothelin (ET), a novel vasoconstrictor peptide, was studied in human vascular tissues by immunohistochemistry. Distinct and diffuse staining for ET-like immunoreactivity was demonstrated in the cytoplasm of vascular endothelial cells, but not in smooth muscle cells or adventitial fibroblasts. The specificity was confirmed by the negative results following immunoabsorption. These findings suggest that human vascular endothelial cells function as an endocrine and/or paracrine cells for ET secretion.

Adult↗

PubMedDate not supplied

Characterization of a chemically reactive propranolol metabolite that binds to microsomal proteins of rat liver.

We have characterized a chemically reactive propranolol (PL) metabolite which binds to proteins in rat liver microsomes. During incubation with rat liver microsomes (1 mg of protein) fortified with an NADPH-generating system, 4-hydroxypropranolol (4-OH-PL) quickly disappeared from the reaction medium, but none of the possible metabolite peaks was detected under the high-performance liquid chromatographic conditions used. The consumption of 4-OH-PL depended on microsomes and NADPH. The reaction was not affected by inhibitors of cytochrome P450 or FAD monooxygenase, but was markedly diminished in the presence of cytosol and ascorbic acid. The effect of cytosol was inhibited by potassium cyanide but not by sodium benzoate or dimethyl sulfoxide, and was also not affected by heating at 60 degrees C for 30 min, suggesting that superoxide (SO) ion was involved in the reaction and that it was blocked by superoxide dismutase (SOD) present in the cytosol. Cu,Zn-SOD, purified from cytosol, effectively mimicked the suppressive effect of cytosol. Incubation of 4-OH-PL in an SO-generating system of xanthine and xanthine oxidase generated 1,4-naphthoquinone (1,4-NQ), which was identified by TLC, HPLC, and GC/MS. 1,4-NQ was also formed in microsomal incubates containing NADPH and small amounts of microsomes (below 0.1 mg of protein). These results indicate that 4-OH-PL is converted by SO, or some reactive oxygen species derived from it, to 1,4-NQ which binds to proteins and is one of the reactive metabolites of PL.

Animals↗

PubMedDate not supplied

Incidence of hepatitis C virus (HCV) antibodies and HCV-RNA in blood donors and patients with liver diseases in the inshore area of the Yangtze River.

The Nantong area is a high risk region for primary hepatocellular carcinoma (PHC) in the inshore area of the Yangtze River. However, no detailed data are available about hepatitis C virus (HCV) infection in this area. We examined the incidences of anti-HCV and HCV-RNA in blood donors with hepatitis B surface antigen (HBsAg)- and hepatitis B core antibody (HBcAb)-negative and patients with chronic liver diseases in the Nantong area at Nantong Medical College, Jiangsu Province, the People's Republic of China. The incidences of HBV markers (HBsAg and/or HBcAb), anti-HCV (C100-3), second generation anti-HCV, HCV-RNA and any marker of HCV in the Nantong area were found to be: 0.0, 0.7, 0.4, 0.2 and 0.7% in donor bloods; 16.9, 0.0, 3.4, 15.7 and 16.9% in patients with acute hepatitis; 82.8, 2.7, 4.8, 7.5 and 10.2% in those with chronic hepatitis; 86.4, 4.5, 9.1, 4.5 and 11.4% in those with liver cirrhosis; 87.5, 6.3, 0.0, 0.0 and 6.3% in those with PHC; and 21.8, 1.3, 1.3, 0.0 and 1.3% in patients without liver diseases, respectively. Although the Nantong area is a high risk region for PHC, these data suggest that HCV infection is not an important aetiological factor for PHC in this area.

Blood Donors↗

PubMedDate not supplied

Plasmapheresis for a schizophrenic patient with drug-induced lupus anti-coagulant.

A 59-year-old patient with schizophrenia developed Sjögren's syndrome. She also presented with the lupus anticoagulant attributed to long-term medication with chlorpromazine. Serial plasmapheresis treatments were performed to decrease the anti-coagulant activity. As a result, the activated partial thromboplastin time was temporarily improved, but the lupus anti-coagulant activity did not change. Because of her unstable emotional state, she continued to require chlorpromazine, but took a low dose of aspirin (87 mg/day) and never manifested any signs of thrombotic events. In view of the potential anti-thrombotic effects of chlorpromazine, it may not be necessary to use plasmapheresis in an attempt to reduce anti-coagulant activity among patients with chlorpromazine-induced lupus anti-coagulant.

Antipsychotic Agents↗

PubMedDate not supplied

Efficacy of lansoprazole against peptic ulcers induced by non-steroidal anti-inflammatory drugs: endoscopic evaluation of ulcer healing.

Beyond the obvious step of limiting use of non-steroidal anti-inflammatory drugs (NSAIDs), the treatment of ulcers induced by NSAIDs remains controversial. We evaluated the efficacy of the proton-pump inhibitor lansoprazole on NSAID-induced ulcers. Ulcers were endoscopically diagnosed in 47 NSAID users. These patients received 30 mg/day lansoprazole, orally, for 6 or 8 weeks (6 weeks for duodenal ulcers and 8 weeks for other ulcers). Ulcer healing was assessed using an established classification system. The presence of immunoglobulin G antibody against Helicobacter pylori was also evaluated. The antibody was present in the sera of 51% of patients (24/47). Most of the ulcers reached scarring stages S1 (healing) or S2 (good healing), and the S2 healing rate was 35%. Two H. pylori seropositive patients did not reach these stages; their ulcers were improved by H. pylori eradication therapy, followed, in one case, by medication with misoprostol. Lansoprazole seemed to be useful for most patients with NSAID-induced ulcers, but a few needed additional treatments.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMedDate not supplied

Antithymocyte globulin for a patient with systemic lupus erythematosus complicated by severe pancytopenia.

The clinical use of antithymocyte globulin is rarely reported in patients with rheumatic diseases. We describe the use of this agent in a patient with systemic lupus erythematosus who concomitantly developed severe pancytopenia. High-dose methylprednisolone therapy had been unsuccessful in controlling either the disease exacerbation or the pancytopenia. Antithymocyte globulin and cyclosporin A were therefore administered to achieve immunosuppression. The exacerbation of disease activity was gradually lessened, except for persistent thrombocytopenia and anaemia. Severe and persistent immunosuppression, however, led to a fatal brain abscess. The combined use of both antithymocyte globulin and cyclosporin A induced potent immunosuppression, and should be confined to selected patients with systemic lupus erythematosus, and administered under detailed monitoring.

Adult↗

PubMedDate not supplied

Expression of beta 1 integrins (very late antigens-4 and -5) on myeloma cells and clinical correlates in patients with multiple myeloma.

beta 1 Integrins are considered to be essential for the differentiation of bone-marrow B cells through an interaction with fibronectin-expressed bone-marrow stromal cells. The expression of very late antigens-4 (VLA-4) and -5 (VLA-5) by CD38bright bone-marrow cells in patients with multiple myeloma was measured by flow cytometry using specific monoclonal antibodies. The percentage of CD38bright bone-marrow cells appeared to correlated with that of bone-marrow plasma cells as judged by examination of bone-marrow smears (r = 0.911, P < 0.0001). Expression of VLA-4 and VLA-5 by CD38bright cells varied between patients, but the expression of VLA-4 was always equal to or greater than that of VLA-5. The ratio of VLA-4 to VLA-5 expression (VLA-4:VLA-5 ratio) was calculated and compared with the clinical features of the myeloma patients. A high VLA-4:VLA-5 ratio (> 2.0) was associated with the presence of plasmacytomas and urinary Bence-Jones protein was more common in this group. No other correlations between the clinical features of the disease and the expression of beta 1 integrins were found.

ADP-ribosyl Cyclase↗

PubMedDate not supplied

Increased soluble CD4 molecules and the role of soluble CD4 production in patients with rheumatoid arthritis.

We investigated the concentration of soluble CD4 molecules (sCD4) in serum, and the mechanism of sCD4 production from T lymphocytes, in patients with rheumatoid arthritis (RA). The concentration of sCD4 molecules was determined using a solid-phase enzyme-linked immunosorbent assay method. Using reverse transcription polymerase chain reaction (RT-PCR) techniques, we studied the presence of alternatively spliced mRNA encoding the transmembrane site of CD4, and the mRNA encoding a conservative region of the CD4 binding site of the human immunodeficiency virus (HIV), in the serum of RA patients. Levels of sCD4 found in RA patients were higher than in normal controls (199 U/ml compared with 8.4 U/ml, respectively), and correlated with additional medical parameters. The results of RT-PCR suggested that the higher sCD4 levels may be due to shedding from the cell membrane after protease digestion, not to alternative splicing or a reaction to viral binding to sCD4.

Adult↗