Imidapril-induced eosinophilic pleurisy. Case report and review of the literature.

We describe an unusual case of a patient with eosinophilic pleurisy associated with long-term administration of imidapril, an angiotensin-converting enzyme inhibitor (ACEI). An 81-year-old woman who had been given imidapril for the treatment of essential hypertension was admitted to our hospital for investigation of persistent low-grade fever, dry cough and difficulty in breathing. Left-sided eosinophilic pleurisy was diagnosed based on eosinophilic pleural effusion and peripheral eosinophilia. Soon after administration of imidapril was discontinued, her clinical symptoms subsided, and there was improvement in both diagnostic imaging and laboratory findings. So far, to our knowledge, this is the first reported case in which ACEI induced eosinophilic pleurisy.

Increased levels of UV-induced protease activity in human UVAP-1 cells exposed to gravity-changing stress: involvement of E-64-sensitive proteases in suppression of UV mutagenicity.

Under the 1G condition, the increase in antipain-sensitive protease activity promptly after UV (mainly 254 nm wavelength) irradiation in cultured human cells is detected and found to be one of the intriguing events involved in suppression of cell mutability. It was found that two cell lines, RSa and its variant UVAP-1 cells are applicable; the former is hypermutable and not susceptible to protease activation, while the latter is hypomutable and susceptible. In the present study it was investigated whether the increase in protease activity by UV irradiation is also observed in hypomutable human UVAP-1 cells exposed to gravity-changing stress and whether the increase is involved in suppression of UV mutagenicity. Exposure of human UVAP-1 cells to gravity-changing stress such as free-fall and parabolic flight prior to UV irradiation resulted in a pronounced increase in protease activity, but not to hypergravity conditions (2 and 10G) prior to UV irradiation. To characterize the proteases, components of lysates from the cells exposed to free-fall prior to UV irradiation were fractionated by high performance liquid chromatography, indicating two separate fractions with highly increased levels of E-64-sensitive protease activity. In the cells treated with E-64 during their exposure to free-fall, K-ras codon 12 base substitution mutation was detected after UV irradiation, although the mutation was not detected after UV irradiation alone. Thus, the increase in E-64-sensitive protease activity may be involved in the suppression of UV mutagenicity in UVAP-1 cells exposed to free-fall.

Induction of apoptosis and ubiquitin hydrolase gene expression by human serum factors in the early phase of acute myocardial infarction.

The physiologic events leading to apoptosis in myocardial infarction and the molecules involved in the death process have not been clarified unequivocally. We developed a method to search for serum factors that induce apoptosis of human cells, using serum obtained from patients within 1 day of the onset of acute myocardial infarction (AMI). Serum factors were found to have the ability to increase the caspase-3 activity levels in human RSa cells, which are susceptible to apoptosis inducers. The factors obtained from AMI patients by elution at about 0.5 mol/L KCl from a dye-ligand column were named AMI-SFs (serum factors from AMI). Electrophoretic analysis showed DNA fragmentation in AMI-SF-treated RSa cells, but not in RSa cells treated with fractions from AMI patients 1 week after clinical onset of illness. AMI-SF-induced DNA fragmentation was also demonstrated by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling analysis, whereas a suppression of fragmentation was seen in RSa cells treated with AMI-SFs in combination with a caspase-3 inhibitor. The increase in caspase-3 activity was not inhibited by neutralizing antibodies to tumor necrosis factor-alpha, interleukin-6, human interferon-beta, or interferon-gamma. Polymerase chain reaction-based messenger RNA differential display and Northern blotting revealed an increase in the messenger RNA expression level of human ubiquitin hydrolase in AMI-SF-treated RSa cells. Antisense oligonucleotides for ubiquitin hydrolase inhibited the increase in caspase-3 activity. These findings suggested that serum from AMI patients in the acute phase contains factors that induce apoptosis, possibly by inducing the expression of the ubiquitin hydrolase gene, at least in the human cells tested.