Invited commentary.
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Disease Susceptibility↗
Biomedical subjects
Hendrik Jan Ankersmit
Publications and source records attributed to Hendrik Jan Ankersmit.
Lipopolysaccharide-induced tumor necrosis factor alpha production and not monocyte human leukocyte antigen-DR expression is correlated with survival in septic trauma patients.
Multiple trauma patients have an impaired immune system and thus frequently develop life-threatening septic complications. Because there is an ongoing debate on which are the most predictive immunologic parameters of clinical outcome, we prospectively studied 19 multiple trauma patients with sepsis (mean age, 38.7 +/- 15.8 years; mean Injury Severity Score, 40.6 +/- 11.6) over a period of 14 days. The following parameters were measured daily after admission to the intensive care unit: ex vivo lipopolysaccharide (LPS)-induced tumor necrosis factor alpha (TNF-alpha) production, monocyte human leukocyte antigen (HLA)-DR expression, constitutive interleukin (IL) 6 secretion, white blood cell count, and C-reactive protein. In addition, procalcitonin, neopterin, LPS-binding protein, and constitutive TNF-alpha secretion were measured every third day. Immediately after trauma, all patients had significantly lower levels of HLA-DR and ex vivo LPS-stimulated TNF-alpha secretion than healthy controls (n = 7; P < 0.001). On the day after clinical diagnosis of sepsis, before any other parameter differed between survivors (n = 13) and nonsurvivors (n = 6), ex vivo LPS-induced TNF-alpha secretion was significantly lower (P < 0.05) in nonsurvivors than in survivors. We conclude that ex vivo LPS-induced TNF-alpha production is an earlier predictor of clinical outcome in multiple trauma patients with sepsis than monocyte HLA-DR expression, constitutive IL-6 secretion, or any other parameter assessed.
Adolescent↗
Apoptosis-specific activation markers in on- versus off-pump coronary artery bypass graft (CABG) patients.
BACKGROUND: The relation of epithelial/endothelial apoptosis and secretion of death-inducing receptors (DIR) in comparison to vascular adhesion molecules is not known in patients undergoing the On- versus Off-pump coronary artery bypass graft (CABG) procedure. METHODS: 30 patients were prospectively included in the study (On- vs. Off-pump CABG, each n = 15). Serum samples were obtained prior to, and 30 minutes, 60 minutes and 24 hours after CABG operation. ELISA was utilized to detect caspase-cleaved cytokeratin-18 (CK18) by means of M30 antibody, soluble VCAM-1, soluble ICAM-1, and soluble DIR TNFR-1 and CD95. RESULTS: Soluble caspase-cleaved CK18 was increased and leveled to initial values at 24 hrs. sICAM-1 showed a significant decrease at 30 minutes and 60 minutes in comparison to preoperative values. sTNFR-1/sCD95 showed a rise that was not significant to preoperative values. CONCLUSION: These results indicate for the first time that epithelial/endothelial apoptosis is occurring in patients undergoing bypass operation, irrespective of the CABG procedure selected.
Apoptosis↗
Endothelin activation and postoperative renal failure after human liver transplantation.
Renal failure is an established risk factor for impaired patient outcome after orthotopic liver transplantation (OLT). As the endothelin pathway is known to be involved in the development of acute renal failure (ARF), we designed a study to clarify its role in ARF following OLT. Twenty consecutive patients with intact kidney function scheduled for their first OLT were prospectively studied. Plasma big endothelin-1 (ET-1) levels were measured before surgery, after graft reperfusion, and on the first and second postoperative day. According to postoperative glomerular filtration rate (GFR), patients were assigned to the acute renal dysfunction group (ARDF) and the non-ARDF group. Each patient's GFR was estimated according to the 4-variable formula used in the modification of diet in renal disease before surgery, daily within the first postoperative week, and at 1, 3, 12, and 24 months after surgery. Postoperative mean big ET-1 levels correlated significantly with the maximum percent decrease of GFR within 3 days after OLT (P < 0.01). The proportion of patients who developed ARDF was significantly correlated to mean postoperative big ET-1 quartiles (P < 0.01). In the ARDF group, the percent decrease of GFR within 24 months was significantly higher (P < 0.05) as compared to the non-ARDF group. In conclusion, patients who develop ARDF immediately after OLT do not fully recover to baseline regarding long-term kidney function. Short-term GFR was significantly correlated with postoperative big ET-1 plasma levels, suggesting renal dysfunction is mediated by the activated endothelin system.
Endothelins↗
Soluble ST2 protein in cardiac surgery: a possible negative feedback loop to prevent uncontrolled inflammatory reactions.
BACKGROUND: Recent reports have demonstrated that cardiopulmonary bypass (CBP) utilization leads to a TH2 cytokine bias in patients undergoing coronary artery bypass grafting (CABG) operation. The relation of soluble ST2 and secretion of IL-10, markers of TH2 T-cell activation, and IL-13 in relation to immunoglobulin isotope production is not known in patients undergoing On- versus Off-pump (CABG) procedure. METHODS: 30 patients were prospectively included in the study (On- vs Off-pump CABG, each n = 15). Serum samples were obtained prior to, and 30 min, 60 min and 24hrs after operation. ELISA was utilized to detect sST2 and IL-10, IL-13 and immunoglobulin isotype production. RESULTS: In both cohorts we could demonstrate a significant rise of ST2 24 hours after the CABG procedure. In the On-pump group ST2 levels (pg/ml) before the operation, at 30 and 60 minutes and after 24 hours were 115.3 +/- 25, 71.2 +/- 15, 114.1 +/- 26 and 4231.9 +/- 520, respectively. In the Off-pump group they were 200.3 +/- 109, 91.2 +/- 20, 137 +/- 29 and 4144.9 +/- 488 (both, p < 0.0001, p < 0.0001, respectively). IL-10 (pg/ml) levels rose from preoperative values of 6.2 +/- 1.6 in the On-pump group and 7.91 +/- 1.8 in the Off-pump group to 33.14 +/- 8.7 and 13.72 +/- 3 after 60 minutes (p 0.0189, p 0.0397, respectively). IL-13 levels and immunoglobulin production did not change significantly within the study period irrespective of the operation procedure used. CONCLUSION: In conclusion, our results demonstrate that sST2 and IL-10, markers of TH2 cytokine producing cells, are increased in CABG operation, irrespective of the procedure selected, and settles a longstanding controversy concerning the shift from Th1 to Th2 cells.
Cardiopulmonary Bypass↗
Thrombophilia associated with anti-CD154 monoclonal antibody treatment and its prophylaxis in nonhuman primates.
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Animals↗
Increased levels of soluble ST2 protein and IgG1 production in patients with sepsis and trauma.
OBJECTIVE: T1/ST2, a member of the interleukin (IL)-1 receptor superfamily, is predominantly expressed on type-2 T helper (Th2) cells but not Th1 cells, and plays a role in cell proliferation and Th2 immune response. The relation of soluble ST2, Th1-Th2 cytokine profile, and immunoglobulin (Ig) production in sepsis and trauma patients is not well known. DESIGN AND SETTING: Case-control study at a university hospital intensive care unit. PATIENTS: Fifteen patients recruited within 24-48 h of diagnosis of sepsis, 13 trauma patients recruited within 24 h after admission to the ICU, 11 patients who underwent abdominal surgery, and 15 healthy volunteers served as control. MEASUREMENTS AND RESULTS: ELISA was utilized to detect serum soluble ST2, IL-2, IFN-gamma, IL-10, and Ig production. Serum levels of soluble ST2 were significantly increased in septic patients (8420+/-2169 pg/ml) as compared with trauma (2936+/-826 pg/ml), abdominal surgery (1423+/-373 pg/ml), and healthy controls (316+/-72 pg/ml; p<0.001, respectively). These results were accompanied by an increase of IgG1 and IgG2 production, and decrease of IL-2 and IFN-gamma synthesis in septic patients. IL-10 was significantly increased in both septic and trauma patients. CONCLUSIONS: Our results demonstrate that soluble ST2, a marker for Th2 cytokine producing cells, is increased in sepsis and trauma patients, and they provide further evidence for a shift from Th1- to Th2-biased cells.
Enzyme-Linked Immunosorbent Assay↗
CDT values are not influenced by epithelial cell apoptosis in chronic alcoholic patients-preliminary results.
Carbohydrate-deficient transferrin (CDT) has been well established as a marker for high alcohol consumption. As studies concerning the specificity of CDT in patients with liver disease have shown controversial outcomes, efforts to illuminate mechanisms leading to impaired CDT specificity in this patient group cannot yet be considered successful. Evidence of apoptosis as examined in 72 alcohol-dependent patients using serum contents of caspase-related M30 monoclonal antibody significantly correlated with aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyl transpeptidase but did not influence CDT levels. These results suggest that impairment of CDT specificity is brought forth by derangement of hepatic metabolism rather than by acute hepatocellular damage.
Alcoholism↗
Aberrant T cell activation and heightened apoptotic turnover in end-stage renal failure patients: a comparative evaluation between non-dialysis, haemodialysis, and peritoneal dialysis.
Patients in end-stage renal disease (ESRD) have a high incidence of bacterial and viral infections. Fifteen non-dialysed (ND), 15 haemodialysed (HD), 15 patients with peritoneal dialysis (PD), and 15 healthy controls were included. T cell proliferation was measured by [3H]thymidine uptake. Apoptosis and cell phenotype were determined by FACS. sTNF-R1, sCD95, interleukin-1beta-converting enzyme (sICE), and interleukin (IL)-10 were measured by ELISA. PHA and CD3-driven T cell proliferation were significantly decreased in ESRD patients. CD3(+), CD19(+) B cells, and percentage of CD4(+) T cells were significantly reduced. Percent memory T cells (CD45RO(+)) and cells undergoing apoptosis (CD95(+)/Annexin V+) were significantly increased in ESRF. Moreover, sCD95, sTNFRI, and ICE were significantly increased. Serum level of IL-10, a Th2 cytokine, was enhanced. These findings strongly suggest that in ESRD patients Th1 T cells are selectively susceptible to undergo apoptosis. This observation provides an additional pathophysiological concept in the genesis of Th2 dominance.
Aged↗
CD32-mediated platelet aggregation in vitro by anti-thymocyte globulin: implication of therapy-induced in vivo thrombocytopenia.
Induction therapy with polyclonal antithymocyte-globulin (ATG) is widely used in the prophylaxis and treatment of acute cardiac-allograft rejection. Thrombocytopenia, however, is a major side-effect of ATG therapy and its mechanisms are poorly understood. The influence of ATG on platelet aggregation was studied aggregometrically, expression of platelet surface activation antigens CD62P and CD63 was determined by flow cytometry analysis, and electron microscopy was utilized to determine thrombocyte morphology. Treatment of platelets with ATG markedly induced aggregation, whereas OKT3 or anti-IL-2R antibodies did not. Furthermore, platelets incubated with ATG featured an up-regulation of the surface activation markers CD62P and CD63, secretion of platelet-bound sCD40L (CD154) and increased signs of aggregation in electron microscopy analysis. The capacity of ATG to induce platelet aggregation was completely blocked by antibodies against the low-affinity Fc IgG receptor (CD32). Since blocking of CD32 abrogates platelet aggregation, we suggest that CD32 plays a crucial role in ATG-induced thrombocytopenia.
Flow Cytometry↗
Transitory immunologic response after implantation of the DeBakey VAD continuous-axial-flow pump.
BACKGROUND: The development of local and systemic infection is a significant risk factor associated with implantation of a ventricular assist device. The immunologic consequence of continuous-flow rotary blood pumps is not known. METHODS: Six male adult patients (mean age 47 plus minus 10.3) with end-stage left heart failure received a DeBakey VAD axial-flow pump for use as a bridge to transplantation. (Four patients underwent transplantation after a mean 115 plus minus 14 days; 2 patients are still waiting for the allograft.) RESULTS: We prospectively monitored T-cell populations and apoptosis-specific aberrant T-cell activation via CD95 triggering and annexin V binding to lymphocytes, identifying T cells undergoing early phases of apoptosis, within the first 10 weeks. Moreover, soluble death-inducing receptors soluble CD95 and soluble tumor necrosis factor-R1 were evaluated by enzyme-linked immunosorbent assay. CONCLUSION: Patients bridged to transplantation by a nonpulsatile ventricular assist device demonstrated an initial pronounced apoptosis-specific immune alteration by increased annexin V binding to CD3 T cells and death-inducing receptors soluble CD95/tumor necrosis factor-R1 (all P <.001). All parameters normalized after 7 weeks to baseline. No blood-borne sepsis was detected, as defined by blood culture, within the first 10 weeks of the cohort study. These results indicate a biphasic immunologic response in patients with end-stage heart failure treated with nonpulsatile ventricular assist devices.
Adult↗