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Biomedical subjects

R A Winchurch

Publications and source records attributed to R A Winchurch.

At least 37 records · Page 2Linked to original sources
PubMed1988

Depressed natural killer cell function in thermally injured adults: successful in vivo and in vitro immunomodulation and the role of endotoxin.

Natural killer (NK) cells mediate host defense against infections and are regulated by interleukin 2 (IL-2) and other factors. We studied NK cell function in burn patients using a 51Cr release assay with K562 target cells. We found that peripheral blood lymphocytes from burn patients had depressed NK activity (target cell lysis = 22.0 +/- 3.1% vs 39.8 +/- 3.2% in healthy volunteers, P less than 0.001) and also a lower response to IL-2 (28.9 +/- 3.8% vs 53.2 +/- 4.3%, P less than 0.001). Thirteen burn patients were randomly assigned to receive either standard therapy or 5 days of intravenous polymyxin B in addition to standard therapy. After 2 weeks, the patients not receiving polymyxin B had a significant decline in peripheral blood NK activity (P less than 0.01) and response to IL-2 (P less than 0.05), while no decline in NK cell activity was seen in patients who received polymyxin B. Sera from burn patients was found to suppress the NK activity of lymphocytes from healthy adults by 5-75%. After using affinity chromatography to remove endotoxin, the sera from burn patients no longer suppressed NK cell activity. Circulating endotoxin appears to be involved in the suppression of NK activity in burn patients.

Adult↗
PubMed1987

Ontogenic variation in acute lethality of cadmium in C57BL/6J mice.

Susceptibility of C57BL/6J mice to the lethal effects of parenterally administered Cd declined as a function of age at exposure. The 7-day LD50 increased from 1.65 mg Cd/kg body wt in 7-day-old mice to 4.08 mg/kg in adult mice. Survival time following treatment with Cd also increased as a function of age. High constitutive concentrations of metallothionein, a transition metal-binding protein, in livers of young mice did not protect against the lethality of Cd. These results suggest that, in the mouse, the interaction between Cd and this metal-binding protein may be affected by age at exposure to this toxic metal.

Aging↗
PubMed1987

Supplemental zinc (Zn2+) restores antibody formation in cultures of aged spleen cells. II. Effects on mediator production.

In vitro antibody production to T-dependent erythrocyte antigens is depressed as a function of age. Supplementation of antibody-forming cultures with the essential trace element zinc restores the capacity of cells from immunodepressed, aged mice to generate an antibody response. Zn2+ produces maximal enhancement of immune function when it is added to the cultures within the first 24 h. Supernatants obtained from cultures supplemented with zinc from 0-24 h contain soluble, nondialyzable factors which support enhanced antibody production in fresh cultures of cells from aged mice. Interleukin 2 levels in the supernatants from Zn2+-supplemented cultures were not increased. However, the levels of interleukin 1 were increased approximately 300% over nonsupplemented controls and these increases corresponded with the ability of the supernatants to support antibody formation. Further studies showed that, in addition to enhancing the production of interleukin 1, Zn2+ enhanced the ability of concanavalin A-activated T cells from aged mice to produce B cell stimulatory factor-1.

Aging↗
PubMed1987

Endotoxemia in burn patients: levels of circulating endotoxins are related to burn size.

With use of a quantitative limulus assay, the levels of circulating endotoxins were examined in a population of burn patients with injuries covering 1% to 88% of the total body surface area (TBSA). In cases in which the injury was less than 20% TBSA, the increases in endotoxins were only 35% as compared with those of normal controls. As the extent of injury increased, the levels of endotoxins also increased: burns between 21% and 40% TBSA showed average increases of over 350% and burns in excess of 40% showed increases of 500%. The relationship between burn size and total endotoxin burden was significant (p = less than 0.01). Time-course studies indicated that in most cases, peak endotoxin levels occurred 3 to 4 days after injury. The data also showed that there was no relationship between the age of the patient and the extent of the endotoxin increase.

Adult↗
PubMed1986

Reversal of postburn immunosuppression with low-dose polymyxin B.

In a randomized study of 28 patients with thermal injury, polymyxin B was administered intravenously in small doses to attempt to block the immunosuppressive effects of endotoxin. When compared with controls, treated patients showed a reduction in septic complications and death, but this reduction is not statistically significant at this time. In vitro measurements of lymphocyte function, however, indicate a statistically significant improvement in the T helper to suppressor ratio, and in the lymphocyte responsiveness to a number of bacterial antigens.

Adult↗
PubMed1985

Burns. Infection and immunology.

The burn wound is successively colonized by gram-positive then gram-negative flora. The reduction of mortality from sepsis in burns depends on our understanding of the chain of events leading to microbial invasion of the burn wound and the host response that follows. These are outlined in this article, together with the current attempts to improve this response in the host.

Adjuvants, Immunologic↗
PubMed1984

Supplemental zinc restores antibody formation in cultures of aged spleen cells.

The in vitro production of antibody to T-dependent antigens is depressed as a function of age. The addition of supplemental zinc to cultures of cells from young adult, middle-aged, and immunodepressed-aged mice enhances antibody production. The responses of young mice are enhanced 30 to 40%, but the responses in cultures from aged mice are increased 5- to 12-fold and the maximum response achieved is often equivalent to that of young, fully competent mice. The addition of zinc at varying times during the culture period suggests that zinc affects early events in the activation of antibody-forming cells.

Aging↗
PubMed1984

Impairment of human lymphocyte function by bile salts.

Since there appears to be an association between depressed lymphocyte function and liver disease, the effect of bile salts on lymphocyte function was determined in vitro. Peripheral lymphocytes from normal volunteers were incubated with varying concentrations of three bile salts (chenodeoxycholate, deoxycholate, or ursodeoxycholate) and stimulated by the mitogens phytohemagglutinin or concanavalin. The three bile salt concentrations used in these experiments were 75, 100, and 250, mumol/L, which are similar to serum levels found in various types of liver disease. Blast transformation, as measured by tritiated thymidine incorporation, was significantly depressed by all three bile salts at all concentrations and with both mitogens. Suppression increased with the higher bile salt concentrations. However, ursodeoxycholate suppressed lymphocyte function significantly less than did either chenodeoxycholate or deoxycholate. These data suggest that elevated serum bile levels associated with liver disease may contribute to immunosuppression and that ursodeoxycholate, an epimer of chenodeoxycholate that is used for gallstone dissolution, depresses lymphocyte function significantly less than does chenodeoxycholate.

Bile Acids and Salts↗
PubMed1983

The preparation of stable phosphorylcholine-erythrocyte conjugates for use in plaque assays.

A method for the preparation of stable phosphorylcholine-conjugated erythrocytes is described. This method employs the formation of active esters of phosphorylcholine hydroxyphenylacetic acid (PC-HPA) and results in coupled red cells which are completely stable for 2-3 weeks. Using this procedure up to 80% of the activity was demonstrable after 6 weeks. Cells coupled with PC-HPA are suitable for the demonstration of anti-idiotype effects in a plaquing assay.

Animals↗
PubMed1983

Prediction of sepsis in the multitraumatic patient by assays of lymphocyte responsiveness.

In vitro lymphocyte response to antigens, mitogens and in mixed lymphocyte culture were studied at intervals after injury in 31 patients with extensive trauma. Mean responses were significantly depressed up to 15 to 20 days. Responses were lower and the duration of suppression longer in those patients who become infected, and the suppression of response preceded the onset of infection. Extremely low responses were found in three patients who later died. This in vitro system is suitable for the serial monitoring of patients, as it reflects the extent of injury, infectious sequelae and prognosis. Its results are quantifiable and avoid the problems associated with repeated skin testing.

Accidents, Traffic↗
PubMed1982

Suppression of lymphocyte function after aortic reconstruction. Use of nonimmunosuppressive anesthesia.

Serial estimations of lymphocyte responses to antigens and mitogens and in mixed lymphocyte culture in 13 major vascular surgical patients were carried out before and after operation, which was performed using anesthetic agents that have been shown not to depress lymphocyte function. All responses were significantly depressed up to five to eight days, and some up to nine to 11 days. Such depression, attributable to surgical trauma, may underline the vulnerability to infection of these patients who are having prostheses inserted.

Aged↗
PubMed1982

Suppressor cell activity after major injury: indirect and direct functional assays.

In vitro responses to streptokinase-streptodornase (SKSD), mumps, and mixed lymphocyte culture (MLC) in 19 burned and 13 multitrauma patients were studied sequentially by lymphocyte tritiated thymidine incorporation and compared to responses of 28 normals. Mean responses to SKSD remained significantly depressed from normal for up to 14 to 28 days following injury: MLC responses, significantly depressed at 48 hours, recovered promptly to normal levels. Because of evidence that the proliferative capacity of the T-cell population to soluble antigens is contained within the inducer subpopulation while both inducer and suppressor subpopulations respond in MLC, the observed increase in MLC responses, coupled with a sustained depression of SKSD and mumps responses, suggests activation of a population of suppressor cells. In a direct assay of suppressor cell function, lymphocytes from three or four multitrauma patients incubated in a two-way MLC with normal lymphocytes significantly suppressed PHA responsiveness, confirming the findings of the direct assay.

Adolescent↗
PubMed1982

Lipopolysaccharide-induced activation of suppressor cells: reversal by an agent which alters cyclic nucleotide metabolism.

The effects of bacterial lipopolysaccharides (LPS) on the suppressor activity of mouse spleen cells were examined. Pretreatment with LPS was shown to induce suppressor activity in vivo and in vitro. Concurrent treatment of spleen cells with LPS and imidazole, an agent which increases the activity of cyclic nucleotide phosphodiesterases and hastens the degradation of cyclic AMP, reversed the suppressor-inducing effects of LPS. In vitro treatment of spleen cells with aminophylline, an agent which inhibits phosphodiesterase activity, had no effect on suppressor activity. The reversal of LPS-induced suppressor activity by imidazole was time-dependent and addition of this agent 20 hr after LPS treatment did not reverse suppression. These data are consistent with the hypothesis that LPS-induced suppressor activity may be mediated via cyclic AMP-dependent pathways.

Aminophylline↗
PubMed1982

Inhibition of graft rejection by LPS: further evidence for effects on T lymphocytes.

The effects of bacterial lipopolysaccharides (LPS) on the growth of allografted lymphoma cells in Balb/c mice were studied. It was determined that the injection of LPS at the time of graft implantation resulted in a transient proliferation and a delay in the rejection of the graft. This effect was not attributable to any enhancement of proliferation of the lymphoma cells by LPS nor to any activity of LPS as a competing antigen or as a polyclonal activator of antibody formation. The in vitro cytotoxicity of peritoneal macrophages from LPS-treated animals against allogeneic lymphoma cells was equal to that of mice not treated with LPS. In vitro proliferation responses of splenic lymphocytes from LPS-treated animals indicated that LPS treatment produced a differential depression of Concanavalin A (Con A) responses but phytohemagglutinin (PHA)-induced responses were elevated significantly. These results suggest that the LPS-induced impairment of cell-mediated immunity involves a subset of Con A reactive T cells whose function is important in allograft rejection.

Animals↗
PubMed1981

The "in vitro skin test": a reliable and repeatable assay of immune competence in the surgical patient.

In vitro blast transformation of human peripheral lymphocytes was tested using standard skin test antigens, the mitogens PHA and Con A, and the mixed lymphocytes reaction. The study group included 15 patients with multiple trauma, 40 with major burns, six following cholecystectomies, six following aortic reconstruction, and 30 normal volunteer controls. Repeated skin testing may sensitive patients to candida and streptokinase-streptodornase (SKSD), and desensitize them to mumps antigen. Blast transformation in response to PPD did not correlate with the clinical status of the patients; similarly, blast transformation in response to stimulation by the mitogens PHA and Con A could not reliably predict the occurrence of septic complications. Reactivity in response to stimulation by the soluble antigens SKSD and mumps and in the one-way mixed lymphocyte reaction accurately predicted the clinical course of patients. This method of "in vitro skin testing" is a reliable and repeatable method of monitoring the immunologic status of patients whose illness or injury requires longitudinal study.

Antigens↗
PubMed1980

Longitudinal assay of lymphocyte responsiveness in patients with major burns.

Serial blast transformation in vitro was measured in peripheral lymphocytes from 38 patients with major thermal injury. Lymphocytes were tested with the antigens streptokinase-streptodornase (SKSD), mumps and purified protein derivative (PPD), the mitogens concanavalin A (Con A) and phytohemagglutinin (PHA), and in the one-way mixed lymphocyte reaction. Statistically significant suppression by the burn injury was noticed in all measurements except response to PHA. One-time measurements were not significantly different between the patients who survived and the patients who did not survive their burn injuries. However, serial determinations of responsiveness to the three natural antigens SKSD, mumps and PPD, as well as the mixed lymphocyte reaction accurately reflected prognosis.

Adolescent↗