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S Kapiotis

Publications and source records attributed to S Kapiotis.

At least 37 records · Page 2Linked to original sources
PubMed2000

Prostaglandin E(1) is able to increase migration of leukocytes through endothelial cell monolayers.

Leukocyte interactions with endothelial cells play an important role during inflammatory processes. Leukocytes pass a monolayer of endothelial cells (ECM) to migrate into the extravascular space. The aim of the current study was to investigate whether prostaglandin E(1) (PGE(1)) influences the process of leukocyte migration. In a prospective controlled study, the influence of prostaglandin E(1) (50-5000 ng/mL) on leukocyte migration through endothelial cell monolayers (n = 7) was investigated. Human umbilical endothelial cells (HUVEC) and/or leukocytes were preincubated with clinically relevant, higher, and lower concentrations of prostaglandin E(1) and the amount of leukocyte migration after 3 h was measured. HUVEC were cultured on microporous membrane filters until achievement of a monolayer for investigation of leukocyte migration. Polymorphonuclear leukocytes (PMNL) were isolated from healthy volunteers and PMNL migration was studied under the influence of PGE(1). In clinically relevant concentrations, PGE(1) was able to increase significantly leukocyte migration through endothelial cell monolayers (205 +/- 7.8%, P < 0.05 compared to control; when treating PMNL alone, migration rate was 120 +/- 9.2% compared to control, ns; only endothelial cell monolayers treated up to 145 +/- 10.2%, P < 0.05 compared to control) showing a dose-dependent effect. In this assay, both cell types (PMNL and ECM) could be treated simultaneously, simulating the clinical situation after an iv administration. In conclusion, PGE(1) is able to increase leukocyte migration through endothelial cell monolayers when both cell types are pretreated. The treatment of either leukocytes or endothelial cell monolayers in the cell coculture showed no significant increase. These findings support the theory that prostaglandins may play a major role during inflammation. Future clinical studies are warranted to confirm this hypothesis.

Adult↗
PubMed2000

Partial inhibition of nitric oxide synthase primes the stimulated pathway of vWF-secretion in man.

Increased release of von Willebrand factor (vWF) has been linked to the pathogenesis of atherosclerosis. For this complex disease, impairment of endothelium-derived, nitric oxide production and impaired vascular relaxation has also been reported. Since endothelially produced nitric oxide (NO) is known to inhibit secretion of the Weibel-Palade bodies in animals, we hypothesized that NO could mitigate vWF secretion. In a randomized, placebo controlled cross-over trial, eight male volunteers received N-monomethyl-L-arginine (LNMMA) to block endothelial NO production or placebo, and vWF release was stimulated by infusing desmopressin in three cumulative doses (0.05, 0.15, 0.4 microg/kg) in both periods. At a threshold dose of 0.l5 microg/kg desmopressin, concomitant partial blockade of NO production resulted in 20% higher levels of vWF (P<0.04). However, maximal vWF release after 0.4 microg/kg desmopressin was unaffected by L-NMMA (Delta7% between periods, P=0.88). These data show the dampening effect of NO production on vWF release in response to threshold concentrations of secretagogues. This may in part explain the higher vWF levels in cardiovascular diseases associated with impaired endothelial NO generation.

Adult↗
PubMed2000

Prostaglandin E(1) does not influence plasmatic coagulation, hepatic synthesis, or postoperative blood loss in patients after coronary-artery bypass grafting.

STUDY OBJECTIVE: To assess whether postoperatively administered prostaglandin E1 (PGE1) might prevent bleeding in patients after coronary artery bypass grafting (CABG). DESIGN: Prospective, randomized, placebo-controlled trial. SETTING: University-affiliated hospital. PATIENTS: 49 patients scheduled for elective CABG surgery. INTERVENTIONS: The PGE1 group received intravenous PGE(1) up to 15 ng/kg/min for 72 hours after surgery, whereas the placebo group received isotonic saline for the same time period. MEASUREMENTS AND MAIN RESULTS: Nine patients (4 in the PGE1 group vs. 5 in the placebo group) had to be excluded because of hemodynamic instability, and 1 in the placebo group because of gastric bleeding. In the remaining 39 patients (20 vs. 19), no significant differences with regard to hemoglobin levels or platelet count could be observed. There was no significant difference between the groups concerning the amount of packed red blood cells, platelet concentrates, or fresh frozen plasma transfused. No significant differences could be observed regarding laboratory markers of coagulation activation or hepatic synthesis either. CONCLUSIONS: PGE1 did not prevent coagulation disturbances and blood loss when administered postoperatively in patients undergoing CABG. The absence of these expected effects might be explained by the concomitant administration of acetylsalicylic acid, whose antiaggregatory acivity seems to exceed the effects of PGE1.

Aged↗
PubMed2000

Thrombus formation on the balloon of heparin-bonded pulmonary artery catheters: an ultrastructural scanning electron microscope study.

OBJECTIVE: To investigate heparin-bonded pulmonary artery catheters with respect to thrombus formation and platelet aggregation at the balloon and the shaft using a scanning electron microscope in critically ill patients. DESIGN: Prospective study. SETTINGS: Critical care unit and research laboratories. PATIENTS: Pulmonary artery catheters were inserted in critically ill patients (n = 10). INTERVENTIONS: Pulmonary artery catheters were removed after 24, 48, 72, or 120 hrs, and the ultrastructure was investigated in specialized research laboratories. MEASUREMENTS AND MAIN RESULTS: Balloon and shaft were investigated using a scanning electron microscopic technique. Area of thrombus formation was quantified using image analysis. Heparin release of the catheters was measured. The frequency of balloon inflations was investigated in in vitro experiments by inflating catheters different times (0, 10, 20, and 30 times). Twenty-four hours after catheter insertion, scanning electron microscopic images showed thrombus formation and platelet aggregation at the site of the balloon. Seventy-two hours after catheter insertion, a thrombus started to detach. The areas of thrombus formation did not differ, but thrombus organization changed dramatically 72 and 120 hrs after catheter insertion. The shaft was colonized by single cells only. Cracks of the balloon could be observed after 72 hrs, whereas no cracks could be found in in vitro controls. In vitro, heparin release of the pulmonary artery catheters decreased significantly after 24 hrs. CONCLUSIONS: Scanning electron microscopic images of heparin-bonded pulmonary artery catheters demonstrate thrombus formation on the balloon 24 hrs after pulmonary artery catheter insertion, increasing dramatically at 72 and 120 hrs. The shaft was colonized by single cells only. The thrombus size is not significantly different during the observation time, but the grade and quality of thrombus formation differ.

Anticoagulants↗
PubMed1999

Rapid, fluorescence-based assay for microtiter plates to test drug influences on neutrophil transmigration through endothelial cell monolayers.

Investigation of drug interactions between blood cells and endothelium is of high interest. The current study describes the development of a rapid fluorescence-based leukocyte transmigration system through endothelial cell monolayers for investigation of drug influences. To test the new assay, endothelial cells were cultured on microporous filters, pore size 3.0 microm, in 96-well-plates. Freshly isolated neutrophils were seeded on endothelial cell monolayers and transmigrated cells were measured after incubation for three hours. Migration of non-stimulated neutrophils through non-stimulated endothelial cell monolayer was used as control and set as 100%. The influence of the non-steroidal anti-inflammatory drug diclofenac was investigated. Assay precision tests were done using intraassay (within-day variability) and interassay (day-to-day variability) controls. Transmigration rate was decreased to 53 +/- 6.8% SD (diclofenac 0.7 microg/mL). Different concentrations showed a dose dependent effect (0.07 microg/mL: 97 +/- 9.5%, 7 microg/mL: 37 +/- 4.7%). Analysis of assay accuracy of the new 96-well-sized transmigration assay showed reliable results (coefficient of variation: intraassay 8.2 %; interassay 11.8%). In conclusion, this new, rapid, and sample saving 96-well-microtiter transmigration assay allows examination of drug influence on neutrophil migration through endothelial cell monolayers. Moreover, this assay can also be used for other cell-cell interactions.

Adult↗
PubMed1999

Evaluation of the automated coagulation analyzer SYSMEX CA 6000.

In the present study the coagulation analyzer SYSMEX CA 6000 (TOA Medical Electronics Co., Kobe, Japan), an analyzer equipped with a photooptical clot detection unit and a cap-piercing system, was evaluated with respect to its technical characteristics in the determination of standard coagulation tests (prothrombin time, activated partial thromboplastin time, thrombin time, fibrinogen, and antithrombin) and in the determination of coagulation single factor activities. In the normal and in the pathological range the intraassay coefficients of variation (CV) and interassay CV for most parameters were below 5% (exceptions: intraassay CV 5.4% for prolonged thrombin time; intraassay CV 9.26% and interassay CV 10.7% for decreased antithrombin; interassay CV 5.62% for fibrinogen in the normal range, intraassay CV 10.1% for fibrinogen greater than 7.0 g/L; intraassay CV 6.36% and interassay CV 11.7% for decreased fibrinogen; interassay CV 11.6% for prolonged activated partial thromboplastin time; interassay CV 6.12% for decreased factor VII). Interference studies with lipemic, icteric, and hemolytic samples showed just minor influences of these abnormal sample characteristics on prothrombin time, activated partial thromboplastin time, fibrinogen, and antithrombin measurements when compared to the results obtained by using mechanical clot detection (STA, Stago Diagnostica, Asnieres-Sur-Seine, France). No carryover was detected in alternating measurements of heparinized (3 U/mL unfractionated heparin) and normal plasma samples. Measurement of the activities of clotting factors V, VII, VIII, and IX showed a good correlation (r=0.993 to r=0.977) between SYSMEX CA 6000 and STA. Our results demonstrate that using SYSMEX CA 6000 analyzer basal routine coagulation testing as well as specialized tests for single factor activities can be performed with satisfactory precision; in particular, the cap-piercing system has no negative effect on the performance of the analyzer.

Adult↗
PubMed1999

The green tea extract epigallocatechin gallate is able to reduce neutrophil transmigration through monolayers of endothelial cells.

Green tea is widely used in Asia and has also become popular in Western countries. The influence of green tea extracts on leukocytes is not well understood. Leukocytes play a crucial role in the process of inflammation. They migrate from the intravascular space into the tissue to attack micro-organisms. The aim of the current study was to investigate the influence of epigallocatechin gallate on leukocyte transmigration through endothelial cell monolayers and thereby evaluate its potential role in the inflammatory process. Human umbilical vein endothelial cells were cultured on microporous membranes to achieve a monolayer. Freshly isolated neutrophils from healthy subjects were measured with a migration assay. The amount of untreated neutrophils migrating through untreated endothelial cell monolayers was used as control and set as 100%. Neutrophils and/or endothelial cell monolayers were pre-treated with epigallocatechin gallate using relevant, as well as higher and lower concentrations. The relevant plasma concentration of epigallocatechin gallate was able to significantly inhibit neutrophil migration through endothelial cell monolayers (69 +/- 6.4% SD; p < 0.05 compared to control), when both cell types (leukocytes and endothelial cell monolayer) were treated. This is similar to the situation after resorption in-vivo. Treating either neutrophils or endothelial cell monolayers alone led to significant reductions in migratory response (only neutrophils treated: 86 +/- 8.1% SD, p < 0.05; only endothelial cell monolayers: 77 +/- 6.1%, p < 0.05). In conclusion, epigallocatechin gallate was identified as a potent inhibitor of leukocyte migration through endothelial cell monolayers. The treatment of both cell types showed an additive effect. Endothelial cells seem to be more affected than neutrophils. Further clinical investigations are necessary to understand the potential clinical consequences.

Catechin↗
PubMed1999

Salicylate inhibits LDL oxidation initiated by superoxide/nitric oxide radicals.

Simultaneously produced superoxide/nitric oxide radicals (O2*-/NO*) could form peroxynitrite (OONO-) which has been found to cause atherogenic, i.e. oxidative modification of LDL. Aromatic hydroxylation and nitration of the aspirin metabolite salicylate by OONO- has been reported. Therefore we tested if salicylate may be able to protect LDL from oxidation by O2*-/NO* by scavenging the OONO reactive decomposition products. When LDL was exposed to simultaneously produced O2*-/NO* using the sydnonimine SIN-1, salicylate exerted an inhibitory effect on LDL oxidation as measured by TBARS and lipid hydroperoxide formation and alteration in electrophoretic mobility of LDL. The cytotoxic effect of SIN-1 pre-oxidised LDL to endothelial cells was also diminished when salicylate was present during SIN-1 treatment of LDL. Spectrophotometric analysis revealed that salicylate was converted to dihydroxybenzoic acid (DHBA) derivatives in the presence of SIN-1. 2,3- and 2,5-DHBA were even more effective to protect LDL from oxidation by O2*-/NO*. Because O2*-/NO* can occur in vivo, the results may indicate that salicylate could act as an efficacious inhibitor of O2*-/NO* initiated atherogenic LDL modification, thus further supporting the rationale of aspirin medication regarding cardiovascular diseases.

Free Radical Scavengers↗
PubMed1999

The mast cell as site of tissue-type plasminogen activator expression and fibrinolysis.

Recent data suggest that mast cells (MC) and their products (heparin, proteases) are involved in the regulation of coagulation and fibrino(geno)lysis. The key enzyme of fibrinolysis, plasmin, derives from its inactive progenitor, plasminogen, through catalytic action of plasminogen activators (PAs). In most cell systems, however, PAs are neutralized by plasminogen activator inhibitors (PAIs). We report that human tissue MC as well as the MC line HMC-1 constitutively produce, express, and release tissue-type plasminogen activator (tPA) without producing inhibitory PAIs. As assessed by Northern blotting, highly enriched lung MC (>98% pure) as well as HMC-1 expressed tPA mRNA, but did not express mRNA for PAI-1, PAI-2, or PAI-3. The tPA protein was detectable in MC-conditioned medium by Western blotting and immunoassay, and the MC agonist stem cell factor (c-Kit ligand) was found to promote the release of tPA from MC. In addition, MC-conditioned medium induced fibrin-independent plasmin generation as well as clot lysis in vitro. These observations raise the possibility that MC play an important role in endogenous fibrinolysis.

Cell Line↗
PubMed1999

Acetaminophen has greater antipyretic efficacy than aspirin in endotoxemia: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To compare the antipyretic efficacy of aspirin and acetaminophen (INN, paracetamol) in 30 male volunteers with the use of endotoxin (lipopolysaccharide) to elicit a standardized febrile response. METHODS: A randomized, double-blind, placebo-controlled trial was conducted in parallel groups. Subjects received an intravenous endotoxin bolus of 4 ng/kg after premedication with either placebo, 1000 mg aspirin, or 1000 mg acetaminophen by mouth. RESULTS: Peak body temperatures were 38.5 degrees C +/- 0.2 degrees C in the placebo group, 37.6 degrees C +/- 0.2 degrees C in the acetaminophen group (P = .001 versus placebo), and 38.6 degrees C +/- 0.2 degrees C in the subjects treated with aspirin (P = .001 versus acetaminophen; P = .570 versus placebo) at 4 hours after lipopolysaccharide infusion. Subjective symptom scores for chills and perception of fever were higher in the placebo group than in the acetaminophen group (chills, 2.5 +/- 0.3 versus 1.0 +/- 0.2, P = .009 and fever, 2.5 +/- 0.2 versus 2.0 +/- 0.2, P = .021). Tumor necrosis factor-alpha, interleukin-6, and interleukin-8 levels rose by several orders of magnitude (P < .001 versus baseline in all groups), without significant intergroup differences. CONCLUSIONS: Acetaminophen was the superior antipyretic drug in endotoxemia compared with aspirin. Treatment with acetaminophen ameliorates subjective symptoms induced by endotoxemia without compromising the humoral response of a subject to endotoxin. This observation has clinical interest and may also help to improve the lipopolysaccharide model, which can be used to test anti-inflammatory and anticoagulatory drugs.

Acetaminophen↗
PubMed1999

Oral contraceptives that contain ethinyl estradiol (0.035 mg) and cyproterone acetate (2 mg) inhibit leukocyte transmigration through endothelial cell monolayers.

OBJECTIVE: To investigate the influence of ethinyl estradiol and cyproterone acetate in oral contraceptives on leukocyte migration through endothelial cell monolayers. DESIGN: Experimental in vitro prospective study. SETTING: An academic research laboratory. INTERVENTION(S): Endothelial cells were cultured on microporous membranes to produce monolayers. Polymorphonuclear leukocytes were used in a previously described migration assay (n = 7). The amount of untreated polymorphonuclear leukocytes that migrated through untreated endothelial cell monolayers was used as a control and set at 100%. In addition, a leukocyte adhesion assay was used. MAIN OUTCOME MEASURE(S): Leukocyte adhesion to and transmigration through endothelial cell monolayers. RESULT(S): Ethinyl estradiol and cyproterone acetate inhibited the migration of polymorphonuclear leukocytes through endothelial cell monolayers significantly (67% +/- 6.4%) when both cell types were treated to simulate in vivo conditions. The adhesion assay produced similar results. CONCLUSION(S): Ethinyl estradiol and cyproterone acetate were identified as potent inhibitors of leukocyte migration through endothelial cell monolayers.

Cell Adhesion↗
PubMed1999

Clinical significance of lupus anticoagulants in children.

OBJECTIVES: To determine the spectrum of associated clinical manifestations and time course of lupus anticoagulants (LA) in children. STUDY DESIGN: Retrospective study of 95 consecutive children (46 boys and 47 girls), with a median age of 5.3 years (range, 1.7 to 17.1 years), diagnosed with presence of LA at a hemostasis referral center; 83 were followed up over a median of 2.9 years (range, 6 weeks to 21.6 years). RESULTS: At diagnosis, 80 of 95 (84%) children were free of symptoms, and presence of LA was found incidentally. Nine children (10%) had bleeding symptoms, 5 (5%) had thrombotic events, and 1 had systemic lupus erythematosus. Among the patients with bleeding, 5 had transient severe hypoprothrombinemia after adenovirus infections, and 3 had thrombocytopenia. None of the children who were initially free of symptoms had bleeding, thrombotic complications, or autoimmune disease subsequently. At follow-up, 48 of 83 (58%) patients had normal activated partial thromboplastin time values after 1.9 years (5 weeks to 19.1 years). Thirty-two (38%) still had activated partial thromboplastin time elevations but did not fulfill all criteria for presence of LA after 3.2 years (7.4 months to 9.3 years). Three (4%) patients, who had presented with thrombosis, had persistent positive LA, anti-cardiolipin, and antinuclear antibodies after 1.4, 2.8, and 7.5 years, respectively. One of these had recurrent thrombosis. CONCLUSIONS: In most children the presence of LA did not lead to clinical complications and was transient. Bleeding occurred with additional hypoprothrombinemia or thrombocytopenia. Thrombosis was rare and strongly associated with persistently positive LA.

Adolescent↗
PubMed1999

Dexamethasone inhibits leukocyte migration through endothelial cells towards smooth muscle cells.

Leukocyte interactions with endothelial cell monolayers (ECM) and smooth muscle cells (SMC) play an important role during inflammatory processes. Several studies describe an inhibitory effect of dexamethasone on polymorphonuclear leukocytes (PMNL), endothelial cell function, and interleukin-1 (IL-1) release. Aim of the current study was to investigate the influence of dexamethasone on leukocyte migration through an endothelial cell monolayer towards SMC-layers stimulated by tumor necrosis factor-alpha (TNF-alpha). Using a recently developed triple chamber migration system, SMC-layers were cultured on the bottom of a 24-well plate. On the upper surface of the first filter, ECM were cultured, the second filter was a collecting filter. The amount of leukocyte migration through ECM towards TNF-alpha-stimulated smooth muscle cell layers with and without dexamethasone-pretreatment was measured using a fluorescence technique. The pretreatment of SMC-layers with dexamethasone reduced the amount of leukocyte migration down to 92 +/- 8.8% (0.001 mM, p=n.s.), to 67 +/- 5.7% (0.01 mM, p<0.05), to 53 +/- 4.6% (0.1 mM, p<0.05), and to 41 +/- 5.0% (1 mM, p<0.05). In conclusion, dexamethasone treatment of smooth muscle cell layers inhibits leukocyte migration through ECM towards smooth muscle cell layers. The inhibition seems to be due to a decrease in IL-1 release. Treatment of all cell types, PMNL, endothelial cells, as well as smooth muscle cell layers, simulating an in-vivo situation, seems to have an additive effect.

Cell Culture Techniques↗
PubMed1999

Salicylate promotes myeloperoxidase-initiated LDL oxidation: antagonization by its metabolite gentisic acid.

The oxidative modification of low density lipoprotein (LDL) may play a significant role in atherogenesis. Tyrosyl radicals generated by myeloperoxidase (MPO) can act as prooxidants of LDL oxidation. Taking into consideration, that monophenolic compounds are able to form phenoxyl radicals in presence of peroxidases, we have tested salicylate, in its ability to act as a prooxidant in the MPO system. Measurement of conjugated dienes and lipid hydroperoxides were taken as indicators of lipid oxidation. Exposure of LDL preparations to MPO in presence of salicylate revealed that the drug could act as a catalyst of lipid oxidation in LDL. The radical scavenger ascorbic acid as well as heme poisons (cyanide, azide) and catalase were inhibitory. The main metabolite of salicylic acid, gentisic acid, showed inhibitory action in the MPO system. Even when lipid oxidation was maximally stimulated by salicylate the LDL oxidation was efficaciously counteracted in presence of gentisic acid at salicylate/gentisic acid ratios that could be reached in plasma of patients receiving aspirin medication. Gentisic acid was also able to impair the tyrosyl radical catalyzed LDL peroxidation. The results suggest that salicylate could act like tyrosine via a phenoxyl radical as a catalyst of LDL oxidative modification by MPO. But the prooxidant activity of this radical species is effectively counteracted by the salicylate metabolite gentisic acid.

Arteriosclerosis↗
PubMed1999

Fosinopril decreases levels of soluble vascular cell adhesion molecule-1 in borderline hypertensive type II diabetic patients with microalbuminuria.

Angiotensin converting enzyme inhibitors (ACE-I) are a mainstay for the treatment of heart failure, and of diabetic microalbuminuria. Recently ACE-I have been found to decrease plasma levels of circulating vascular cell adhesion molecule-1 (cVCAM-1) in patients with congestive heart failure. As increased cVCAM-1 levels are pathognomonic for diabetics with microangiopathy, we investigated the effects of ACE-I on plasma levels of cVCAM-1, intercellular adhesion molecule (cICAM-1), and cE-selectin in microalbuminuric diabetics. In addition, the effects of ACE-I on plasma levels of plasminogen activator inhibitor (PAI-1) and of tissue plasminogen activator (TPA) were studied. Fosinopril (10 mg/day) was administered over 12 weeks to 11 microalbuminuric patients with non-insulin-dependent diabetes mellitus (NIDDM). As expected, baseline plasma concentrations of cE-selectin, cICAM-1, and cVCAM-1 were markedly higher in patients than in healthy control subjects (n = 82; P < .001). PAI-1 levels in NIDDM were similar to those in control subjects, whereas TPA levels were about 25% lower in patients than in control subjects (P = .013). Serum levels of cVCAM-1 decreased by -19% (CI: -25% to -13%) after treatment with fosinopril (P = .003) and were no longer different from those of the control group. In contrast, plasma levels of cE-selectin, cICAM-1, PAI-1, and TPA were unaffected. As expected microalbuminuria decreased by -44% (CI: -65 to -22; P = .004). In conclusion, fosinopril lowered cVCAM-1 levels along with microalbuminuria in NIDDM. This may represent a novel mechanism of action of ACE-I in diabetes-associated endothelial dysfunction. Whether decreased VCAM-1 expression is responsible for the observed reduction in microalbuminuria, deserves further investigation.

Adult↗
PubMed1999

Activation of endothelium by immunotherapy with interleukin-2 in patients with malignant disorders.

Treatment with intravenous recombinant human interleukin-2 (rh IL-2) is frequently accompanied by the capillary leak syndrome and disturbances of the coagulation system. Although the exact mechanisms are still not fully understood, the involvement of the endothelium is proven. This investigation aimed to elucidate more precisely the role of the endothelium in the generation of IL-2-based side-effects. In nine tumour patients receiving intravenous rh IL-2, parameters characterizing endothelial cell activation as well as activation of the coagulation system were evaluated. A significant increase of the circulating endothelial leucocyte adhesion molecule-1 (cELAM-1) and the vasoconstrictor peptide endothelin-1 (ET-1) was observed (P<0.05), indicating activation of endothelial cells. The simultaneous increase of tissue-plasminogen activator and plasminogen activator inhibitor type-1 during therapy (P<0.05) corroborated this observation. A decrease in platelet count parallelled by an increase of fibrin degradation products, the prolongation of partial thromboplastin time, and the decrease of fibrinogen (P<0.05) suggested the development of disseminated intravascular coagulation (DIC), induced by activated endothelium and intensified by transient hepatic failure. We concluded that activation of the endothelium mediated by IL-2 was accompanied by a loss of endothelial integrity and capillary leak. The activated endothelium can trigger DIC via activation of the coagulation cascade. The increased ET-1 might act as an endogenous counter-regulator of the disadvantageous haemodynamic side-effects induced by IL-2.

Blood Coagulation↗
PubMed1999

IgG subclass reactivity to human cardiac myosin in cardiomyopathy patients is indicative of a Th1-like autoimmune disease.

Studies performed in mice together with the demonstration of increased levels of heart-specific autoantibodies, cytokines and cytokine receptors in sera from cardiomyopathy (CMP) patients argued for a pathogenic role of autoimmune mechanisms in CMP. This study was designed to analyse the presence of IgG anti-heart antibodies in sera from patients suffering from hypertrophic and dilatative forms of CMP as well as from patients with ischaemic heart disease and healthy individuals. Patients' sera were analysed for IgG reactivity to Western-blotted extracts prepared from human epithelial and endothelial cells, heart and skeletal muscle specimens as well as from Streptococcus pyogenes. The IgG subclass (IgG1-4) reactivity to purified human cardiac myosin was analysed by ELISA. While sera from CMP patients and healthy individuals displayed comparable IgG reactivity to a variety of human proteins, cardiac myosin represented the prominent antigen detected strongly and preferentially by sera from CMP patients. Pronounced IgG anti-cardiac myosin reactivity was frequently found in sera from patients with dilatative CMP and reduced ventricular function. ELISA analyses revealed a prominent IgG2/IgG3 anti-cardiac myosin reactivity in CMP sera, indicating a preferential Th1-like immune response. Elevated anti-cytomegalovirus, anti-enterovirus IgG titres as well as IgG reactivity to nitrocellulose-blotted S. pyogenes proteins were also frequently observed in the group of CMP patients. If further work can support the hypothesis that autoreactivity to cardiac myosin represents a pathogenic factor in CMP, specific immunomodulation of this Th1- towards a Th2-like immune response may represent a promising therapeutic strategy for CMP.

Adolescent↗