Collagenolytic metalloenzymes of the human neutrophil. Characteristics, regulation and potential function in vivo.
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Blood Vessels↗
Biomedical subjects
S J Weiss
Publications and source records attributed to S J Weiss.
Consensual norms regarding patient involvement.
A stratified sample of 72 nurses, physicians and members of the general public met together in small tripartite dialogue groups each month for 20 months, in order to mutually identify health care behaviors that effectively involve patients in their own health care. Content analysis of 200 hours of verbatim transcripts from the dialogue sessions yielded 1245 patient involvement behaviors. These behaviors were rated by all subjects for their degree of importance within the normative health care relationship through use of a Likert-type inventory. Analysis of the 656 behaviors from the inventory which were classified as essential for effective patient involvement produced 44 clusters, with inter-item correlations ranging from 0.80 to 0.95. Further reduction of the 44 clusters indicated six core clusters, suggesting key norms that existed regarding effective involvement of patients in their own care. Salient norms centered on overt contracts in health relationships, egalitarian communication between patient and professional, patient access to broad-based information, tailoring of treatment programs, self-care and lifestyle modification. The lack of congruence between these norms and the realities of health care is discussed.
Contracts↗
Assay of the extracellular hydrogen peroxide pool generated by phagocytes.
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Cell Separation↗
Activation of the endogenous metalloproteinase, gelatinase, by triggered human neutrophils.
Triggered human neutrophils degraded denatured type I collagen (gelatin) by releasing and activating the latent metalloenzyme, gelatinase. The ability of the neutrophil to activate this enzyme was significantly, but not completely, inhibited by agents known to inhibit or scavenge chlorinated oxidants generated by the H2O2/myeloperoxidase/chloride system. A direct role for chlorinated oxidants in this process was confirmed by the ability of reagent HOCl to activate the latent enzyme in either the cell-free supernatant or in a highly purified state. Gelatinase activity was also expressed by triggered neutrophils isolated from patients with chronic granulomatous disease. The amount of gelatinolytic activity expressed by the patients' cells was similar to that released by normal neutrophils that were triggered in the presence of antioxidants. Thus, human neutrophils have the ability to activate gelatinase by either an HOCl-dependent process or an uncharacterized oxygen-independent process. The ability of the neutrophil to directly regulate this enzyme suggests an important role for the metalloproteinase in physiologic and pathophysiologic connective tissue metabolism.
Enzyme Activation↗
Oxidative regulation of neutrophil elastase-alpha-1-proteinase inhibitor interactions.
Triggered human neutrophils were able to maintain released elastase in an active form in the presence of purified alpha-1-proteinase inhibitor (alpha-1-PI), serum or bronchoalveolar lavage fluid (BAL). The accumulation of free elastase activity was associated with a decrease in the ability of the alpha-1-PI to inhibit porcine pancreatic elastase, an increase in proteinase activity associated with alpha-2-macroglobulin, and the oxidation of alpha-1-PI to a molecule containing four methionine sulfoxide residues. Neutrophils used both hypochlorous acid and long-lived N-chloroamines to oxidize the alpha-1-PI, but hypochlorous acid was preferentially used for suppressing the activity of the antiproteinase over short distances whereas the N-chloroamines were effective even when the phagocytes and alpha-1-PI were physically separated. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of purified alpha-1-PI, serum, or BAL that had been incubated with triggered neutrophils revealed that the released neutrophil elastase was not complexed with the antiproteinase and that a portion of the alpha-1-PI had undergone proteolysis. These data suggest that the presence of free neutrophil elastase as well as inactive, oxidized, and proteolyzed alpha-1-PI in fluids recovered from inflammatory sites in vivo could be directly mediated by triggered neutrophils alone.
Amino Acids↗
Oxygen, ischemia and inflammation.
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Animals↗
Neutrophil-mediated solubilization of the subendothelial matrix: oxidative and nonoxidative mechanisms of proteolysis used by normal and chronic granulomatous disease phagocytes.
Both normal and chronic granulomatous disease (CGD) neutrophils were able to degrade the subendothelial matrix secreted by human endothelial cells via an elastase-dependent process. In the absence of the plasma antiproteinase, alpha-1-proteinase inhibitor (alpha-1-PI), normal neutrophils protect their released elastase from inactivation by using the chlorinated oxidants hypochlorous acid and endogenous N-chloroamines to suppress the antiproteinase's activity. In contrast, CGD neutrophils were unable to generate either class of chlorinated oxidant or to inactivate the porcine pancreatic elastase inhibitory capacity of alpha-1-PI unless the cells were supplemented with exogenous hydrogen peroxide. Despite the reliance of normal neutrophils on chlorinated oxidants to inactivate alpha-1-PI, neutrophils triggered in the presence of agents that block the generation of these reactive species continued to degrade the subendothelial matrix at a suppressed but significant rate in the presence of a 50-fold excess of the antiproteinase. The continued solubilization of the matrix by normal neutrophils was not due to the incomplete inhibition of oxidant generation because triggered CGD neutrophils were also able to degrade the matrix in the presence of excess alpha-1-PI. If CGD neutrophils were stimulated in the presence of an exogenous source of H2O2 and alpha-1-PI, the proteolytic potential of the cells was identical to that observed with normal stimulated neutrophils. We conclude that normal neutrophils can enhance their ability to degrade the subendothelial matrix by oxidatively protecting elastase from inactivation by alpha-1-PI but both normal and CGD neutrophils possess non-oxidatively linked mechanisms for sequestering and using elastase to mediate proteolytic effects in the presence of native antiproteinase.
Blood Proteins↗
Psychophysiologic effects of caregiver touch on incidence of cardiac dysrhythmia.
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Arrhythmias, Cardiac↗
Effects of supplementing hypothermic crystalloid cardioplegic solution with catalase, superoxide dismutase, allopurinol, or deferoxamine on functional recovery of globally ischemic and reperfused isolated hearts.
We evaluated whether supplemental pharmacologic interventions that altered formation or degradation of reactive oxygen metabolites, when added to hypothermic crystalloid cardioplegic solution (procaine-free St. Thomas' Hospital solution), alter postischemic function of isolated rabbit hearts. Hypoxic, substrate-free cardioplegic solutions cooled to 27 degrees C were perfused through isolated rabbit hearts for 5 minutes before and after an uninterrupted 2 hour period of global ischemia at 27 degrees C. Hearts were then reperfused with standard buffer for 1 hour at 37 degrees C. In some experiments, the cardioplegic solution was supplemented with the following: superoxide dismutase (30 micrograms/ml; degrades superoxide anion); catalase (1.7 micrograms/ml; degrades hydrogen peroxide); allopurinol (1 mmol/L; inhibits xanthine oxidase); or deferoxamine (Desferal, 0.5 mmol/L; selectively chelates ferric iron). Postreperfusion contractile parameters of supplemented hearts, including left ventricular pressure development and its first derivative, left ventricular compliance, spontaneous heart rate, and coronary vascular resistance, were statistically compared to data obtained from hearts arrested with unsupplemented cardioplegic solution. Catalase supplementation provided statistically significant improvement of most functional parameters; somewhat less protection was obtained with allopurinol. Deferoxamine provided little added protection except for the ability to prevent ischemia-induced increases of coronary vascular resistance. There was no evidence of added protection by superoxide dismutase. The data suggest that an important component of ischemia-induced cardiac cell damage in an asanguineous setting is hydrogen peroxide-dependent, and interventions that either inhibit production of superoxide anion or degrade hydrogen peroxide offer best protection. They may be clinically efficacious additives to crystalloid cardioplegic solutions.
Allopurinol↗
Oxidative autoactivation of latent collagenase by human neutrophils.
The pathological destruction of collagen plays a key role in the development of inflammatory disease states affecting every organ system in the human body. Neutrophils localized at inflammatory sites can potentially degrade collagen by releasing a metalloenzyme, collagenase, which is stored in a latent inactive form. Triggered human neutrophils were shown to release and simultaneously activate their latent collagenase. The activation of the latent enzyme was coupled to an oxidative process that required the generation of a highly reactive oxygen metabolite, hypochlorous acid. Oxidative regulation of latent collagenase activity may be important in the pathogenesis of connective tissue damage in vivo.
Enzyme Activation↗
The influence of discourse on collaboration among nurses, physicians, and consumers.
The aim of this study was to determine whether ongoing discussion among nurses, physicians, and consumers influenced their collaborative beliefs and behavior. A stratified experimental sample of 72 professionals and consumers met in small, multidisciplinary groups on a monthly basis for 2 years to discuss health care relationships. Prior to the onset of these groups, and after their conclusion, the experimental sample, a randomly selected control group of 72 persons, and a matched control group of 72 persons all completed the Management of Differences Exercise, the Multidimensional Health Locus of Control Scales, and the Health Role Expectations Index. Contrary to predictions, the experimental group (M = -6.85) declined more than controls (M = -4.63, p less than .05) in their beliefs regarding the value of shared versus physician-dominated responsibility for health care and increased more (M = 1.58 versus M = -.53, p less than .007) in their beliefs that powerful individuals such as physicians influence the consumer's health status. Results indicate that ongoing discourse may have enhanced traditional, status quo beliefs regarding the authority and power of the physician rather than fostering collaborative values.
Adolescent↗
Involvement of hydrogen peroxide and hydroxyl radical in the 'oxygen paradox': reduction of creatine kinase release by catalase, allopurinol or deferoxamine, but not by superoxide dismutase.
The objective of this study was to test the hypothesis that cytotoxic oxygen metabolites participate in lytic cardiac cell damage, detected as creatine kinase release, upon reoxygenation of hypoxic, isolated buffer-perfused hearts (oxygen paradox). Perfusate additives included: superoxide dismutase (30 mg/l); catalase (2 mg/l); deferoxamine (0.5 mM); and allopurinol (1 mM). Creatine kinase release upon reoxygenation was reduced, to levels not significantly different from nonhypoxic controls, by adding either catalase, allopurinol or deferoxamine to the buffer during hypoxia. Reduced creatine kinase leakage was not accompanied by parallel preservation of ventricular function or coronary vascular resistance. Administration of catalase during hypoxia was superior to administering it only during reoxygenation. Treatment with catalase during both hypoxia and reoxygenation provided no more protection than administration only during hypoxia. The data suggest that an important component of hypoxia-induced cardiac cell damage is due primarily to hydrogen peroxide, which may then form hydroxyl radical. Superoxide anion plays an important role as a precursor of these species, but added superoxide dismutase alone did not significantly reduce creatine kinase loss. The data also suggest that damage resulting in creatine kinase release upon reoxygenation occurs during oxygen deprivation, and it is mediated in part by cytotoxic oxygen metabolites.
Allopurinol↗
Treatment of Brucella canis and Brucella abortus in vitro and in vivo by stable plurilamellar vesicle-encapsulated aminoglycosides.
Stable plurilamellar vesicles (SPLVs) entrapping aminoglycosides were used to treat infections due to Brucella species (Brucella canis and Brucella abortus). SPLV-entrapped antibiotics effectively eliminated internalized B. canis in cultures of resident murine peritoneal macrophages and internalized B. abortus in cultures of resident guinea pig peritoneal macrophages. In vivo studies demonstrated that SPLV-entrapped aminoglycosides administered to B. canis-infected mice and B. abortus-infected guinea pigs effectively eliminated bacteria from infected organs. The dosage schedule used involved two intraperitoneal administrations of SPLV-entrapped aminoglycosides at three-day intervals. The results demonstrate the superiority of SPLV-entrapped aminoglycosides to free aminoglycosides in effecting elimination of facultative intracellular bacteria in vitro and in vivo. The use of SPLVs as a drug carrier has broad application to treatment of infections due to other organisms.
Aminoglycosides↗
Lethal, potentially lethal, and nonlethal damage induction by heavy ions in cultured human cells.
In the fields of high-LET radiotherapy and space radiation safety it is important to know the relative probabilities with which a cell whose nucleus is struck by a heavy ion will be damaged or killed. Experiments were performed in which synchronous cultured human T-1 cells (presumptive HeLa) were irradiated with natural alpha particles of energy approximately 3.5 MeV at various times after mitotic selection up to the middle of S phase. Nuclear-area histograms were determined as a function of time after mitosis under conditions identical to those used for irradiation. The efficiency with which one particle passing through the nucleus killed a cell was found to be 0.14-0.20. This value was extrapolated to experimental cell survival data obtained when asynchronous cultured human cells were irradiated with He, Li, B, C, N, O, Ne, Ar ions of energy 6.58 or 5.5 MeV/amu, and the cell killing efficiency was found to be in the broad range of 0.5-1.0 under single-hit conditions. Similarly irradiated cells were examined for colony-size distribution by an image analysis technique, and it was found that the loss of large colonies was dose and LET-dependent in a systematic way. Dose-response data suggest two predominant subpopulations, resistant and sensitive cells, and it appears that the sensitive population is affected by single-hit kinetics. The single-hit coefficient for the induction of inherited slow growth varied with LET in a similar way to that for survival. The action cross section for this form of heritable damage appears to be comparable to the geometric cross section of the cell nucleus.(ABSTRACT TRUNCATED AT 250 WORDS)
Alpha Particles↗
Proton stoichiometry associated with human neutrophil respiratory-burst reactions.
Control of the intraphagosomal pH in neutrophils may be of importance in creating a microbicidal environment by regulating the activity of the O2-.-generating NADPH oxidase and the lysosomal enzymes discharged into this compartment. In this study, we examined the proton stoichiometry associated with the primary enzymatic reaction underlying the respiratory burst. A preparation of the neutrophil-derived, membrane oxidase consumed NADPH and generated O2-. with a stoichiometry of 1 NADPH:2 O2-. When the enzymatically produced O2-. was prevented from undergoing dismutation, net protons were released in an approximate 1:2 stoichiometry with O2-. generated. In contrast, when O2-. was allowed to dismutate to H2O2, net protons were consumed in a 1:1 stoichiometry with the accumulated H2O2. Thus, the delta pH associated with the NADPH oxidase-dependent production of O2-. was dictated by the fate of the generated radical. The consumption of the oxidase-generated H2O2 by the lysosomal enzyme myeloperoxidase resulted in the formation of HOCl which was trapped in the presence of taurine as the N-chloro derivative. The ratio of chlorinated product formed to H+ consumed was 1:1. The implications of these results are discussed in terms of the known intraphagosomal pH changes that occur following neutrophil stimulation. We conclude that the O2-.-generating oxidase plays a dual role in the phagosome by simultaneously creating an oxidizing environment that optimizes pH-dependent microbicidal processes.
Cell Fractionation↗
Quantitative and temporal characterization of the extracellular H2O2 pool generated by human neutrophils.
The extracellular H2O2 concentration surrounding stimulated human neutrophils was continuously quantitated with a sensitive, H2O2-detecting electrode. Following stimulation of neutrophils with phorbol myristate acetate, opsonized zymosan particles, or N-formyl-Met-Leu-Phe, the extracellular H2O2 concentration rapidly increased and maintained steady state conditions before falling to undetectable levels in a manner that was dependent on the triggering agent used. Total extracellular H2O2 accumulation for each stimulus was quantitated as the integral of the H2O2 concentration with respect to time. H2O2 accumulation in the extracellular milieu was unaffected by the addition of superoxide dismutase, whereas exogenous catalase or myeloperoxidase completely consumed the released H2O2. Analysis of H2O2 metabolism by neutrophils revealed that stimulus-dependent differences in the size of the extracellular H2O2 pool may be partially attributable to differences in hypochlorous acid generation by the H2O2, myeloperoxidase, chloride system. Finally, both the concentration of H2O2 in the extracellular space and its utilization by myeloperoxidase could be diminished in the presence of an extracellular target cell. These data indicate that the ability of a triggering agent to stimulate the neutrophil to generate H2O2 and release myeloperoxidase, coupled with the characteristics of a target cell population, control H2O2 metabolism in effector-target cell interactions.
Catalase↗
The effect of transition modules on new graduate adaptation.
The purpose of this study was to determine the effectiveness of educational modules to aid new graduate nurses in adapting to the work environment. An experimental group of new graduates (n = 63) and their controls (n = 58) from eight hospitals were given Corwin's Role Conception Scale, Seeman's Powerlessness Scale, Benner's Clinical Skills Inventory, and Munson's Job Satisfaction Index to measure adaptation at entry to work and 6 months later. The effects of the educational modules were determined by the adaptation measures, cognitive tests, and a Nursing Service Questionnaire. After 6 months in the work setting, the experimental group had less discrepancy between their desired and existing level of clinical skill (p less than .05) and a greater orientation to bureaucratic expectations than controls (p less than .01), as well as an increase in job satisfaction (p less than .05) and a decrease in role deprivation (p less than .05). In addition, the impact on turnover saved hospitals an average of $3,178 for every 10 new graduates they hired.
Adaptation, Psychological↗
A cost-benefit analysis of a smoking cessation program.
Smoking cessation programs are usually evaluated in terms of the percentage of participants who have stopped smoking at least 6 months after the program's completion. This paper shows how a relatively low rate of behavior change may actually result in a high ratio of benefits to costs. Cost-benefit analysis is done for a specific program but the procedures and cost estimates are generalizable to other smoking cessation programs. Benefits to the firm included reduced costs of insurance and the savings due to employee absenteeism and disability. Costs included the program costs as well as the opportunity costs of the participants. Data from the literature and from the specific program are combined to form conclusions about the effectiveness of the program.
Absenteeism↗