Bacterial toxin-induced cytokine production studied at the single-cell level.
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Bacterial Proteins↗
Biomedical subjects
S Nagy
Publications and source records attributed to S Nagy.
Input impedance and peripheral inhomogeneity of dog lungs.
Tracheal pressure, central airflow, and alveolar capsule pressures in cardiac lobes were measured in open-chest dogs during 0.1- to 20-Hz pseudorandom forced oscillations applied at the airway opening. In the interval 0.1-4.15 Hz, the input impedance data were fitted by four-parameter models including frequency-independent airway resistance and inertance and tissue parts featuring a marked negative frequency dependence of resistance and a slight elevation of elastance with frequency. The models gave good fits both in the control state and during histamine infusion. At the same time, the regional transfer impedances (alveolar pressure-to-central airflow ratios) showed intralobar and interlobar variabilities of similar degrees, which increased with frequency and were exaggerated during histamine infusion. Results of simulation studies based on a lung model consisting of a central airway and a number of peripheral units with airway and tissue parameters that were given independent wide distributions were in agreement with the experimental findings and showed that even an extremely inhomogeneous lung structure can produce virtually homogeneous mechanical behavior at the input.
Airway Resistance↗
Longitudinal examination of teachers' burnout in a school district.
Teachers in a rural school district were administered the Maslach Burnout Inventory three times over a five-year period. Teachers scoring high on emotional exhaustion and low on personal accomplishment were classified as "experiencing burnout." Across the three waves, the proportion of teachers meeting these criteria for burnout were 7%, 11%, and 11%, respectively. By grade, burnout was noted among 3%, 8%, and 9%, respectively, over time for senior high-school teachers; 7%, 7%, and 11% for junior high-school teachers; and 9%, 17%, and 12% for elementary school teachers. Interventions must consider grade-taught and are probably most cost-effective for elementary school. It is important to establish norms across time and across school settings to determine high-risk groups deserving interventions.
Alabama↗
Effects of FK506 and cyclosporin A on cytokine production studied in vitro at a single-cell level.
Mononuclear cells obtained from human blood were mitogen or antigen activated in vitro in the presence or absence of FK506 or cyclosporin A (CsA). Cytokine production was studied at a single-cell level by ultraviolet (UV) microscopy of fixed permeabilized cells using cytokine-specific monoclonal antibodies (mAb). Phenotypic characterization of the monokine-producing cells was achieved by two-colour immunofluorescent staining. Cytokine production after antigen activation with Staphylococcus aureus enterotoxin A (SEA) was significantly reduced. FK506 or CsA inhibited SEA-induced tumour necrosis factor-alpha (TNF-alpha) production both in monocytes (P less than 0.01) and in lymphocytes (P less than 0.001), at a drug concentration of 1-25 ng/ml for FK506 and 100-500 ng/ml for CsA. Lymphocyte synthesis of interleukin-2 (IL-2), interferon-gamma (IFN-gamma) and TNF-beta after SEA activation was also significantly reduced by either of the drugs. In contrast, endotoxin-induced monokine production (TNF-alpha and IL-6) after lipopolysaccharide (LPS) stimulation was unaffected by FK506 or CsA even when added in concentrations as high as 1000 ng/ml. When the cells were stimulated by phorbol ester (phorbol 12-myristate 13-acetate, PMA) plus calcium ionophore (ionomycin), FK506 and CsA inhibited, in a dose-dependent manner, the production of IL-2, IL-4, IL-5, IFN-gamma and TNF-alpha. The 50% inhibitory concentration (IC50) for FK506 or CsA on the cellular synthesis of the various cytokines varied between 0.6 and 1.0 ng/ml and 20 and 60 ng/ml, respectively. Further stimulation by addition of anti-CD28 mAb to the cultures resulted in an augmented IL-2 and IFN-gamma production which was resistant to both FK506 and CsA. This report delineates extensive similarities between the two drugs in mechanisms of immunosuppression by blockade of identical interleukin production. Depending on the mode of cell activation the two drugs inhibited not only cytokine production in lymphocytes but also antigen-induced monokine (TNF-alpha) production in macrophages, although the optimal immunomodulatory effect of FK506 was achieved at a concentration approximately 50-fold lower than that of CsA.
Antigens, CD↗
FK 506 and cyclosporine inhibit antigen- or mitogen-induced monokine and lymphokine production in vitro.
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Cells, Cultured↗
Studies on the relationship between xanthine oxidase and histamine release during intestinal ischemia-reperfusion.
Recent studies have demonstrated a connection between xanthine oxidase-generated reactive oxygen intermediates and histamine release during ischemia-reperfusion. In the present work, the effect of modulation of the endogenous histamine level on the xanthine oxidase activity was examined during the reperfusion of a canine ileal segment following a 2 hr of complete ischemia. The xanthine oxidase activity and the plasma histamine level peaked simultaneously at the beginning of reperfusion, reaching mean values of 14.9 nmol/ml/min and 12.1 nmol/l, respectively. Pretreatment with aminoguanidine, a blocker of diamine oxidase (histaminase), resulted in significantly higher levels of histamine during reperfusion, but this elevation was not accompanied by a further increase in xanthine oxidase activity. Pretreatment with the mast cell stabilizer cromolyn significantly diminished the rise in plasma histamine level, with an unchanging activity of xanthine oxidase. No significant alteration could be observed in the postocclusive activity of xanthine oxidase following the intra-arterial administration of 0.5, 1, or 5 nmol of histamine during the last 10 min of the ischemic period. These data suggest that the amount of histamine liberated during reperfusion does not result in a further increase in the xanthine oxidase activity. The release of histamine is not a cause, but rather an effect of the elevated activity of intestinal xanthine oxidase.
Animals↗
Nonlinearity and harmonic distortion of dog lungs measured by low-frequency forced oscillations.
The nonlinearity of lung tissues and airways was studied in six anesthetized and paralyzed open-chest dogs by means of 0.1-Hz sinusoidal volume forcing at mean transpulmonary pressures (Ptp) of 5 and 10 cmH2O. Lung resistance (RL) and elastance (EL) were determined in a 32-fold range (15-460 ml) of tidal volume (VT), both by means of spectrum analysis at the fundamental frequency and with conventional time-domain techniques. Alveolar capsules were used to separate the tissue and airway properties. A very small amplitude dependence was found: with increasing VT, the frequency-domain estimates of RL decreased by 5.3 and 14%, whereas EL decreased by 20 and 22% at Ptp = 5 and 10 cmH2O, respectively. The VT dependences of the time-domain estimates of RL were higher: 10.5 and 20% at Ptp = 5 and 10 cmH2O, respectively, whereas EL remained the same. The airway resistance increased moderately with flow amplitude and was smaller at the higher Ptp level. Analysis of the harmonic distortions of airway opening pressure and the alveolar pressures indicated that nonlinear harmonic production is moderate even at the highest VT and that VT dependence is homogeneous throughout the tissues. In three other dogs it was demonstrated that VT dependences of RL and EL were similar in situ and in isolated lungs at both Ptp levels.
Airway Resistance↗
Effect of antioxidant therapy on cyclooxygenase-derived eicosanoid release during intestinal ischemia-reperfusion.
Conflicting data have been reported on the relationship between reactive oxygen intermediates and the formation of oxygenase-derived eicosanoids. Plasma levels of prostacyclin (PGI2, measured as the stable metabolite 6-keto-PGF1 alpha) and thromboxane A2 (TxA2, measured as TxB2) in the effluent blood of a canine ileal segment were determined following 1 or 2 h of ischemia. The synthesis of both eicosanoids was significantly stimulated during reperfusion, but extension of the ischemic interval from 60 to 120 min was not followed by a further increase. The role of oxidants potentially involved in the process was investigated by using materials that inactivate the xanthine-oxidase-generated intermediates. Previous studies on the same in vivo animal model had demonstrated the effectiveness of antioxidant therapy in reducing the postischemic histamine release. There was no significant alteration in the amount of eicosanoids synthesized following oral allopurinol, catalase, dimethylsulfoxide, mannitol or desferrioxamine treatment. Intravenously administered allopurinol, however, significantly elevated the postischemic 6-keto-PGF1 alpha/TxB2 ratio. The results suggest that these antioxidants at doses inhibitory to histamine liberation are not effective in influencing the postischemic eicosanoid release. Intravenously administered allopurinol could exert a potentially beneficial effect through a mechanism other than the blockade of xanthine oxidase.
Allopurinol↗
The effects of FK 506 on cytokine production are dependent on the mode of cell activation.
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Antibodies↗
Histamine release during intestinal ischemia-reperfusion: role of iron ions and hydrogen peroxide.
Reactive oxygen intermediates (ROI) play a major role in the mucosal damage developing during the reperfusion period following intestinal ischemia. We have shown previously that histamine (H) release is related to the ROI generated by xanthine oxidase during intestinal ischemia-reperfusion. The present study sought to determine the possible chain of events leading to H liberation. The artery supplying a segment of the ileum was occluded for 2 hr in 51 anesthetized dogs, and plasma levels of H were determined radioenzymatically in the venous effluent. Catalase was applied to scavenge hydrogen peroxide; dimethylsulfoxide and mannitol were used as hydroxyl radical scavengers; the role of catalytically active iron was assessed by using desferrioxamine. Pretreatment with either catalase or desferrioxamine, but not with dimethyl sulfoxide or mannitol, was effective in reducing the postocclusive H release. The results provide further in vivo evidence that ROI are causative agents in H liberation during reperfusion of the ischemic gut. Hydrogen peroxide can interact with catalytically active iron and generate highly reactive oxidants, which in turn are responsible for H release. The exact nature of these oxidants is still uncertain.
Animals↗
Selected risk factors in adolescent suicide attempts.
This study examined stress, depression, attempted suicide, and knowledge of common signs of potential suicide in Alabama adolescents. A modified version of the National Adolescent Student Health Survey (NASHS) was administered to 3,803 eighth- and tenth-grade public school students during the fall of 1988. The incidence of stress, depression, and attempted suicide was analyzed by gender, ethnicity, locale (urban vs. rural), and participation in sexual intercourse and use of alcohol. Chi-square tests were used to determine if there were significant differences between groups. Findings indicated that females were at greater risk than were males. Both males and females who engaged in sexual intercourse and alcohol consumption were at greater risk than were abstainers. When analyzed by ethnicity, white adolescents who engaged in these behaviors were at significantly greater risk than were those who abstained; differences were not as pronounced for black youth. Comparisons on the knowledge scale indicated that females scored better than males, whites scored better than blacks, and urban students scored better than rural students. The data suggest that many adolescents are having difficulty coping with stress and depression, and that those who are engaging in various types of risk-taking behavior are at greater risk for depression and suicide.
Adolescent↗
A comparison of AIDS and STD knowledge between sexually active alcohol consumers and abstainers.
Effective curricula should influence knowledge levels of all students, including high-risk populations. In this study, a modified version of the National Adolescent Student Health Survey was administered to a group of eighth and 10th grade students (N = 3,803) exposed to a curriculum designed to improve AIDS and STD knowledge levels. The analysis examined the influence of gender, ethnicity, alcohol use, and sexual activity as they related to AIDS and STD knowledge. Findings indicated poor knowledge scores on STD items, with no significant differences on group comparisons. Comparisons of AIDS knowledge scores indicated significant differences based on gender, ethnicity, and behavior. Females scored higher than males, whites scored higher than blacks, and abstainers from sexual activity and alcohol scored higher than their active counterparts. Results suggest current educational efforts are not equally effective. Future educational initiatives should be sensitive to group membership.
Acquired Immunodeficiency Syndrome↗
Modeling of low-frequency pulmonary impedance in dogs.
The mechanical impedance of the lungs (ZL) was measured in open-chest dogs with small-amplitude pseudorandom volume oscillations between 0.125 and 5 Hz, at mean transpulmonary pressures (Ptp) of 0.2, 0.4, and 0.8 kPa. At the lowest frequencies, the pulmonary resistance showed a marked negative frequency dependence and mirrored the changes in the reactance with altered Ptp. The ZL data were evaluated on the basis of two models, each containing the same airway compartment with a resistance and an inertance. The tissue impedance (Zti) in model 1 was represented with two compliances and a resistance (L. E. Mount. J. Physiol. Lond. 127: 157-167, 1955), whereas in model 2 a two-parameter formulation implying rate-independent dissipated work and frequency-dependent elastance (J. Hildebrandt. J. Appl. Physiol. 28: 365-372, 1970) was employed. The estimation of model parameters showed that model 2 was superior to model 1 in both fitting performance and parameter insensitivity to weighting in the fitting criterion. The model 2 coefficients of damping and elastance, characterizing the real and imaginary parts of Zti, respectively, depended on the lung distension and were closely correlated. Although ZL exhibited a slight dependence on the peak-to-peak volume excursion, at a given oscillatory volume no inconsistency with linear tissue viscoelasticity was detected.
Animals↗
The role of histamine release in shock.
More than 80 years after its discovery and nearly 70 years after its first being implicated in the mechanism of shock, the precise role of histamine (H) in the pathophysiology of the condition remains to be determined. The prevailing view over the decades has been that H is a noxious mediator contributing to the fatal outcome of shock. An adequate assessment of its role has long been hampered by the lack of a sufficiently sensitive and specific method for the measurement of H and by deficiencies of design in many studies. We now know that H is released in all types of shock. In low-output, high-resistance states, as in hypovolemic and cardiogenic shock, its effect (contrary to previous notions) appears to be beneficial, probably through the inhibition of excessive vasoconstriction and through a positive inotropic effect. In endotoxin shock the results are conflicting, but seem to indicate that H is not a lethal factor. In human septic shock, patients who died had higher H levels. The role of H release in the various forms of shock, both experimental and human, clearly needs an adequate, critical reevaluation, in carefully designed and executed studies using satisfactory methodology.
Histamine Antagonists↗
A canine model of hyperdynamic sepsis induced by intestinal ischemia.
A hyperdynamic sepsis model was developed in dogs. It is based on a 3-hour clamping of the arteries supplying the middle portion of the jejunum. The ensuing sepsis has a course of several days, during which the animals were studied in the conscious state. 2/3 of the animals developed a sustained 32-108 per cent increase in cardiac output, and survived 7 days or more. In the other 1/3 of the animals, the cardiac output was lower than the control value and all these animals died within 5 days. There were no differences between the two groups in other parameters examined. Sepsis caused a steady, slight decrease in mean arterial pressure, an increase in heart rate, and leukocytosis. The plasma levels of epinephrine and norepinephrine showed a sustained, significant elevation. The level of thromboxane B2 was high only on the first day of sepsis, and that of plasma renin activity on the first 2 days. Necrosis and edema of jejunal villi were demonstrated histologically in the early period. Hemocultures were positive in only 5 of 11 animals examined, suggesting the predominant role of absorbed toxins. This model simulates human sepsis well and is suitable for the study of pathophysiologic mechanisms in hyperdynamic sepsis.
Alkaline Phosphatase↗
Oxygen free radical-induced histamine release during intestinal ischemia and reperfusion.
Acute mesenteric ischemia is highly lethal and therefore a serious problem for surgery and intensive care medicine; accordingly its pathophysiology warrants further study. Oxygen free radicals (OFR) play a role in the intestinal mucosal damage that develops during reperfusion after ischemia. Histamine (H) is generally released in various types of tissue ischemia. The link between H release and OFR has only been studied in in vitro systems. We tested the hypothesis that OFR may be involved in H release following reperfusion of the ischemic gut. The artery supplying a segment of the ileum was occluded for 1 or 2 h in anesthetized dogs. On reperfusion, a release of H into the venous effluent of the segment was demonstrated. Pretreatment of the animals with allopurinol (an inhibitor of xanthine oxidase), or with MTDQ-DA [6,6'-methylene-bis(2,2-dimethyl-4-methanesulfonic acid sodium-1,2-dihydroquinoline)], a superoxide anion scavenger, or with a combination of allopurinol and MTDQ-DA resulted in an inhibition of H release. We conclude that OFR may play a role in the local H release following intestinal ischemia.
Allopurinol↗
Mood state changes of women as a function of regular aerobic exercise.
The present study examined mood states of aerobic exercisers before and after completing a 15-wk. program. The subjects (ages 18 to 36 yr.) were 86 women enrolled in activity classes at a large state school in the southeast. Subjects were initially classified according to previous exercise habits. Analysis indicated both groups of frequent and infrequent exercisers were similar in mood states. Participation in regular exercise did not significantly change or enhance the mood states from pretreatment measures. Pretest measures of mood states provided poor prediction of posttest measures, indicating extreme variability in subjects' scores.
Adolescent↗
Relations between preventive health behavior and hardiness.
To estimate the relationship between hardiness and preventive health behaviors a hardiness scale and a health hazard appraisal were administered to 211 college students. Multiple regression analysis indicated that modest amounts of variance on the hardiness measures were explained by the components of the health-hazard appraisals. Indications are that the concepts of hardiness and preventive health behavior are related and need further clarification.
Adult↗