Human heart-type cytoplasmic fatty acid-binding protein as an indicator of acute myocardial infarction.

Human heart-type cytoplasmic fatty acid-binding protein (HH-FABPc) has been proposed as an early biochemical indicator of acute myocardial infarction (AMI). However, skeletal muscles also contain HH-FABPc identical to that found in the heart. Before HH-FABPc can be clinically employed as an indicator of AMI, its content in various tissues other than the heart must be known. Accordingly, we measured the HH-FABPc content of various human muscles and organs, using a sandwich enzyme-linked immunosorbent assay (ELISA) for HH-FABPc. HH-FABPc was abundant in the ventricles (0.46 mg/g wet weight and 1.5% of the cytoplasmic protein in the left ventricle), while the atria contained slightly less HH-FABPc (0.25 mg/g wet weight and 0.7% of the cytoplasmic protein in the left atrium). Of the skeletal muscles tested, the diaphragm contained about one-quarter of the HH-FABPc content of the heart, but other skeletal muscles contained very low levels of this protein. Other than the muscles, the kidneys contained less than one-tenth of the HH-FABPc in the heart, and negligible amounts were found in the liver and small intestine. The distribution of HH-FABPc in the heart and skeletal muscles was comparable to that of cardiac-specific creatine kinase (CK-MB) activity, and was inverse to the distribution of myoglobin. The plasma myoglobin/HH-FABPc ratio, determined in patients with AMI and those without AMI, closely reflected that in the heart and skeletal muscles. These findings indicate that HH-FABPc may be useful as a specific indicator of AMI, and the plasma myoglobin/HH-FABPc ratio could provide valuable information for the diagnosis of AMI.

Luminol-independent chemiluminescence by phagocytes is markedly enhanced by dexamethasone, not by other glucocorticosteroids.

The effect of several glucocorticosteroids on the generation of reactive oxygen species (ROS) was examined. The ROS assessed were O-2, H2O2, OH., and chemiluminescence (CL) (determined in the presence or absence of luminol), generated by both opsonized zymosan-stimulated neutrophils or monocytes and by the xanthine-xanthine oxidase system. Except for luminol-independent CL, only high concentrations (10(-4) M) of steroids could decrease each ROS. In contrast, luminol-independent CL generation in the phagocyte system was increased in a dose-dependent manner by the addition of dexamethasone, but not by any other steroid. Further, in lymphocyte cultures stimulated with Con A for four days, luminol-independent CL generation was demonstrated and enhanced by the addition of dexamethasone, although CL generation was not detected in the absence of dexamethasone. These findings provide evidence that CL does not always represent light specific to ROS, and they suggest the possibility that dexamethasone induces emission of light at sites of inflammation.

Effects of liposomal superoxide dismutase on human neutrophil activity.

Study of the effects of liposomal bovine copper superoxide dismutase on human polymorphonuclear neutrophils with respect to production of active oxygen species, chemotaxis and random migration, or bacterial killing show that no significant interference with neutrophil function is observed at levels far exceeding the clinical doses used in the treatment of various pathologies.

Decreased oxygen radical generation by neutrophils from patients with measles presumably owing to activation of suppressor T lymphocytes.

The capacity for the generation of oxygen radicals by polymorphonuclear leukocytes (PMNs) was assessed in 29 patients with measles and in control groups. Patients with secondary bacterial infections showed a significantly decreased generation of oxygen radicals; this abnormality did not persist for more than 2 months after disease onset. Normal PMNs incubated with T lymphocytes from these measles patients generated significantly fewer oxygen radicals than those incubated with T cells from either control group. However, normal PMNs incubated with non-T lymphocytes from these measles patients produced normal oxygen radical levels. In addition, irradiation above 1,500 rads of T lymphocytes abrogated the suppressive effect of T cells on PMNs. On the other hand, these abnormal findings were not observed in patients with measles but without secondary bacterial infections. The secondary bacterial infections sometimes seen in measles patients may result from a decrease in oxygen radical generation, presumably induced by the suppressive activity of the T lymphocytes of the patients.

Effect of liposomal-encapsulated superoxide dismutase on active oxygen-related human disorders. A preliminary study.

Liposomal-encapsulated superoxide dismutase was clinically applied to patient showing an increase in neutrophil active oxygen generation, and those with diseases such as severe rheumatoid arthritis (RA), Crohn's disease and progressive systemic sclerosis (PSS) in which presence of a plasmatic clastogenic factor has been demonstrated. Liposomal SOD injection (2.5 mg twice a week) resulted in marked remission in 12 out of 16 patients with active Behcet's disease. The drug was impressively effective on patients with intestinal Behcet. Remission rates in the other diseases was 7 out of 8 mucocutaneous lymphnode syndrome (MCLS, Kawasaki disease) 3 out of 5 dermatitis herpetiformis, IgA linear bullous dermatosis or severe cement dermatitis, 4 out of 9 active and severe RA, 3 out of 3 PSS, 4 out of 4 Crohn's disease, 3 out of 4 colitis ulcerosa, and 2 out of 2 unresponsive (hemolytic) anemia. To be emphasized was that three severe active RA patients and two terminal-stage PSS patients with dyspnea due to lung fibrosis showed dramatic improvement after administration of liposomal SOD. In addition, in 13 out of 15 malignant neo plastic patients including cancer, malignant lymphoma and leucemia who were receiving radiotherapy (total dose, more than 4000 rads) and chemotherapy including anthracycline analogs (total over 450 mg/m2) and bleomycin, the drug also prevented the appearance of myocardiac injury and fibrosis, sometimes seen as a consequence of chemotherapy. Liposomal SOD, which shows no toxicity, has various advantages compared to free SOD preparations, and is highly and broadly applicable to various clinical disorders.

Decrease in generation of reactive oxygen species by neutrophils from patients with infectious mononucleosis: role of suppressor T lymphocytes.

We assessed the generation of reactive oxygen species (ROS: O2-, H2O2, OH . , chemiluminescence) by neutrophils and monocytes from six patients with infectious mononucleosis, ten patients with other viral diseases, and ten normal controls. Neutrophils from infectious mononucleosis patients showed markedly decreased generation of all reactive oxygen species, compared with the two control groups; this abnormality persisted for four to eight weeks after disease onset. Monocytes from these patients generated normal levels of ROS. Normal neutrophils incubated with T lymphocytes from infectious mononucleosis patients generated significantly less of each ROS than did those incubated with T cells from either control group. T cell-mediated suppression of ROS generation required both OKT4+ cells from infectious mononucleosis patients and OKT8+ cells from either patients or normals. We conclude that the generation of reaction oxygen species in neutrophils is suppressed in patients with infectious mononucleosis, at least in part, by interacting subsets of T lymphocytes.