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Biomedical subjects

R M Keane

Publications and source records attributed to R M Keane.

12 recordsLinked to original sources
PubMed1994

Postoperative immunological function and jaundice.

The effects of operative trauma and obstructive jaundice on systemic immunity were studied in a rat model, using the delayed-type hypersensitivity response to 2,4-dinitro-1-fluorobenzene as a measure of systemic immune responsiveness. Midline laparotomy caused a significant decrease in the mean(s.e.m.) delayed-type hypersensitivity response 1 week after operation (4.6(1.3) versus 19.0(2.2) per cent for controls). The response returned to control levels by 2 weeks (14.6(3.1) per cent). Common bile duct ligation and division resulted in a significantly depressed hypersensitivity response at 2 and 3 weeks (6.8(2.0) and 8.4(1.6) per cent respectively). The expected decrease in the response at 1 week in these animals was not observed (mean(s.e.m.) 12.7(2.7) per cent), suggesting a possible role for the normal liver in the induction of postoperative immune depression. Impaired function of the reticuloendothelial system was induced in non-jaundiced animals by Kupffer cell ablation following intraportal infusion of lambda-carrageenan. A similar prevention of postoperative immune hyporesponsiveness was observed (mean(s.e.m.) 10.4(1.0) versus 10.4(1.6) per cent for controls). Hepatic Kupffer cells play an important role in the induction of postoperative immune depression.

Animals↗
PubMed1993

Perioperative immune modulation.

BACKGROUND: The effects of operative trauma on systemic immunity were studied. The relative effects of skin incision and of breaching the peritoneum were determined. In addition, the role of the antiendotoxic agent taurolidine in preventing postoperative immune suppression was assessed. METHODS: Systemic immune responsiveness was measured as the delayed-type hypersensitivity (DTH) response to 2-4 dinitro l-fluorobenzene (DNFB) with an in vivo rat model. The effect of both laparotomy and taurolidine on the hepatic Kupffer cell population was determined by immunohistochemistry. RESULTS: This study confirmed that cellular immunity is significantly depressed after laparotomy (15.5%; range, 2.5%-24.0%) compared with unoperated controls (26.77%; range, 9.2%-38.0%). Opening the peritoneum appeared to be a critical factor in inducing this immunosuppression, in which animals undergoing a similar midline incision without opening of the peritoneum displayed minimal alteration in their DTH response (20.5%; range, 0.85%-41.5%). In addition, intraperitoneal administration of taurolidine in the perioperative period prevented this decrease in postoperative DTH response. Kupffer cell numbers were increased after intraperitoneal administration of taurolidine, compared with animals treated with intraperitoneal saline solution or unoperated controls. CONCLUSIONS: These findings confirm the presence of an operatively induced decrease in immune responsiveness and suggest that entering the peritoneum is an important factor in the induction of this effect. In addition, administration of taurolidine acts to prevent the impact of laparotomy on DTH response, possibly by preventing perioperative portal endotoxemia.

Animals↗
PubMed1990

Substrate and inhibitor studies with human gastric aspartic proteinases.

The separation of pepsin isoenzymes 1, 2, 3 and 5 (gastricsin) in human gastric juice was effected by chromatography on Mono Q ion-exchanger, and slow-moving proteinase was purified to homogeneity by using a modified procedure incorporating a novel affinity-chromatography step. The pH-activity profiles of these enzymes with mucus glycoprotein and basement-membrane substrates were determined; the profiles for pepsin 2 were noticeably different, and, in general, the pH optima for the hydrolysis of basement membrane were more acidic. Pepsin 1 expressed larger specificity constants (kcat./Km) than pepsin 3 with a series of synthetic peptide substrates, reflecting greater binding (smaller Km) by pepsin 1. Inhibitor studies at pH 1.7 and 4.5 with a series of P2-substituted lactoyl-pepstatins implied that valine at position P2 was optimal for inhibiting pepsins 1, 2 and 3 but detrimental for pepsin 5, whereas lysine at position P2 was tolerated well by pepsin 5 but not by pepsins 1, 2 and 3. The potency of lactoyl-pepstatin with lysine at position P2 did not increase as a function of pH. P2-substituted lactoyl-pepstatins failed to show any inhibitory selectivity among pepsins 1, 2 and 3.

Basement Membrane↗
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

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↗
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↗