Potential Mediator of Inflammation: PHAGOCYTE-DERIVED OXIDANTS SUPPRESS THE ELASTASE-INHIBITORY CAPACITY OF ALPHA1-PROTEINASE INHIBITOR IN VITRO

Human polymorphonuclear leukocytes, monocytes, or pulmonary alveolar macrophages, stimulated in vitro by phorbol myristate acetate (PMA), released reactive oxygen species able to suppress the elastase inhibitory capacity (EIC) of human serum. Immunoelectrophoresis using antibodies against α₁-proteinase inhibitor (α₁-Pi) and elastase showed that inactivation of α₁-Pi was responsible for the decreased serum EIC. Treatment of phagocyte-inactivated serum with a reducing agent (dithiothreitol) resulted in significant recovery of EIC, suggesting that α₁-Pi had been oxidatively inactivated. Serum EIC was partially protected by superoxide dismutase or catalase. Hydrogen peroxide alone had no effect on serum EIC. Thus, neither H₂O₂ nor O₂⁻ alone, but a product of the two, may have oxidatively inactivated α₁-Pi. In support of the foregoing, neutrophils or monocytes from a patient with chronic granulomatous disease failed to produce detectable levels of O₂⁻ after incubation with PMA. These cells also failed to suppress serum EIC. In the case of PMA-stimulated polymorphonuclear leukocytes or monocytes, extracellular myeloperoxidase may have also played a role in α₁-Pi inactivation since serum EIC was partly protected by azide, cyanide, or the depletion of extracellular chloride. Indeed, in a cell-free system consisting of purified myeloperoxidase, a glucose oxidase-H₂O₂-generating system, and Cl⁻, the EIC of human serum or purified α₁-Pi could also be suppressed. Omission of any single reactant prevented this effect, as did NaN₃ or catalase, suggesting that enzymatically active myeloperoxidase and H₂O₂ were necessary. Immunoelectrophoresis of myeloperoxidase-inactivated serum showed that, as before, inactivation of α₁-Pi was responsible for the decreased EIC. Treating myeloperoxidase-inactivated serum with dithiothreitol led to significant recovery of EIC, again suggesting that oxidative inactivation of α₁-Pi had occurred. Oxidative inactivation of α₁-Pi in the microenvironment of inflammatory cells, at sites of acute or chronic inflammation, may allow proteases released from these cells to damage adjacent connective tissue components more readily.     

In vitro interaction of scrapie agent and mouse peritoneal macrophages

Scrapie brain homogenate was mixed with mouse peritoneal macrophages in vitro. After 2 h of incubation at 37 degrees, a portion of the scrapie infectivity was associated with macrophages. In contrast, very little infectivity was associated with kidney cells that had been exposed to scrapie brain homogenate. After incubation of the scrapie brain homogenate-macrophage mixture at 4 degrees rather than 37 degrees, a reduced quantity of infectivity was associated with the macrophages. These result show that in vitro incubation, the scrapie agent was associated with macrophages, and the data suggest that phagocytic activity was involved.     

Relevance of personality traits to adjustment in group living situations

The study replicates and extends recent work on personality determinants of adjustment. Personality traits and adjustment criteria were selected for relevance to one type of real-life setting (public housing for the elderly that includes a senior center). Personality traits were measured by observer ratings; criteria, by self-report of respondents and perceptions of them by other residents and staff. In concurrent and longitudinal analyses controlling effects of competence and social status, personality traits accounted for significant and meaningful variance in all criteria, and the salience of particular traits varied across criteria. The results are consistent with earlier studies regarding the importance of extraversion and neuroticism to subjective well-being and suggest that they are relevant also to adjustment as perceived by others. The additional traits of congeniality, culture, and nosiness/gossip were related to both inner and outer adjustment measures in the type of situations studied.     

Immunological profile of amyotrophic lateral sclerosis patients and their cell-mediated immune responses to viral and CNS antigens

The `immunological profile' of amyotrophic lateral sclerosis (ALS) patients was established from standard tests for B- and T-cell function. This showed no significant difference from age and sex-matched other neurological (CNS) disease controls and normal subjects. Immune complex (IC) levels in ALS serum differed significantly from normal controls but not from CNS controls. There was no relation between the various indices of immune activity of IC levels and the clinical disability of the ALS patient or progression of the disease. Distribution of complement-fixing antibodies to poliovirus was similar in sera of ALS and control groups. The in vitro cell-mediated immune responses to poliovirus, however, were significantly greater in ALS patients than in CNS controls and were inversely related to the ALS disability score. Poliovirus has not been demonstrated in the CNS or extra-CNS tissues of ALS patients by conventional means but, if latent or defective poliovirus or related virus were present, this could account for sensitization and a possible autoimmune mechanism. ALS patients exhibited in vitro cellular immunity to ALS and normal CNS subfractions. These responses were not related to the ALS disability score or progression of the disease and probably represent epiphenomena.     

Abortive infection of human diploid cells by murine cytomegalovirus

Inoculation of human diploid cells (WI-38) with murine cytomegalovirus (MCMV) did not result in the synthesis of any infectious virions. However, morphological changes typical of the cytopathic effects (CPE) of MCMV were detectable within 12 hr of infection. The CPE included rounding, swelling, and detachment of cells. The nuclei of infected cells were enlarged, and intranuclear inclusions were visible by May Grunwald-Giemsa staining and by the indirect fluorescent-antibody test. All cells infected at a multiplicity of infection of 3 showed CPE, and these cells could not be passaged successfully. Cell lysates and exhausted media from infected WI-38 cultures did not produce any CPE in WI-38 cells. The virus absorbed to WI-38 cells with the same efficiency as to mouse embryo fibroblast cells (MEF). Samples of MCMV in which virus infectivity for MEF cells had been inactivated by ultraviolet irradiation or by exposure to 56 C failed to produce any of the above signs. MCMV-specific CPE did not occur in the presence of actinomycin D (1 mug/ml) or puromycin (20 mug/ml), but 5'-fluoro-2'-deoxyuridine at 1 x 10(-4)m did not prevent CPE or the development of intranuclear inclusions.     

Ego-defense or cognitive consistency effects on environmental evaluations.

Numerous investigators have commented upon the sanguine evaluations of their living environments which are given by elderly people. The discrepancy between residents' and observers' evaluations suggests the involvement of ego defense or dissonance reduction. Insofar as this is true, old people's evaluations should become more negative when their efforts to move to a more desirable setting meet with sucess. This hypothesis was tested with the original group of applicants to one housing project for the elderly and cross-validated 9 years later with the original group of applicants to a different project. In both cases the hypothesis was supported. Applicants who were selected to move to new housing became more negative in their evaluations of housing than applicants who were not selected to move.     

Antiviral activity of arildone on deoxyribonucleic acid and ribonucleic acid viruses.

Arildone (3 micro/ml) reduced the replication of murine cytomegalovirus, Semliki Forest virus, vesicular stomatitis virus, and coxsackievirus A9 by 64, 68, 94, and 98%, respectively. When the plaque reduction method was used to evaluate the antiviral effect for the viruses, a concentration of 3 to 5 micrograms/ml yielded a 50% reduction in plaque numbers. The effect of arildone on virus replication was greatest when the drug was present from the time of inoculation. The effectiveness decreased as the time interval from the inoculation of the virus to the addition of the drug increased. The removal of the drug from infected cells by washing readily reversed the effect, and viral replication resumed at a significant level. Infectivity of these viruses was not inactivated by the drug. Tissue culture cells used for viral growth and assay grew well in arildone (3 micrograms/ml), with cell yields that were comparable to those for cultures in the absence of drug. At 3 micrograms/ml there were minimal effects of the drug on the uptake of 3H-labeled amino acids and [3H]-thymidine into cells. Furthermore, incorporation of these precursors was not affected. However, there was a reduction in uptake of [3H]uridine into the acid-soluble pool and a concomitant reduction in incorporation into acid-insoluble counts.