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Objectives: The authors sought to compare outcomes of patients with myocardial infarction and cardiogenic shock (CS) treated with percutaneous coronary intervention (PCI) with or without intra-aortic balloon pump (IABP) support according to final epicardial flow in the infarct-related artery., Background: A routine use of IABP is contraindicated in patients with myocardial infarction and CS. There are no data regarding the subpopulation of patients who may benefit from such support besides patients with mechanical complications of myocardial infarction., Methods: Prospective nationwide registry data of patients with myocardial infarction and CS treated with PCI between 2003 and 2014 were analyzed. Patients were initially stratified into 2 groups according to final infarct-related artery Thrombolysis In Myocardial Infarction (TIMI) flow grade after PCI: those with successful primary PCI (TIMI flow grades 2 or 3) and those with unsuccessful primary PCI (TIMI flow grades 0 or 1). Outcomes of patients with or without IABP treatment in each group were analyzed and compared., Results: In the unsuccessful PCI group, patients in whom IABP was applied had lower in-hospital, 30-day, and 12-month mortality. IABP support in this group of patients was an independent predictor of lower 30-day mortality (hazard ratio [HR]: 0.72; 95% confidence interval [CI]: 0.59 to 0.89; p = 0.002). Conversely, in patients with successful PCI, IABP was an independent predictor of higher 30-day mortality (HR: 1.18; 95% CI: 1.08 to 1.30; p = 0.0004)., Conclusions: IABP is associated with a lower risk of 30-day mortality in patients with myocardial infarction complicated by CS, in whom primary PCI was unsuccessful., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study aimed to investigate the 5-year clinical follow-up of the HYBRID (Hybrid Revascularization for Multivessel Coronary Artery Disease) trial., Background: The HYBRID trial, the only randomized study involving thorough analysis of outcome after the 2 procedures, suggested that hybrid coronary revascularization (HCR) is feasible in selected patients with multivessel coronary disease referred for conventional coronary artery bypass grafting (CABG). There are currently no long-term outcome data from randomized trials in this setting., Methods: A total of 200 patients with multivessel coronary disease referred for conventional surgical revascularization were randomly assigned to undergo HCR or CABG. The primary endpoint was the occurrence of all-cause mortality at 5 years., Results: Nine patients (4 in HCR and 5 in CABG group) were lost to the 5-year follow-up. Finally, 191 patients (94 in HCR and 97 in CABG group) formed the basis of this study. The groups were well balanced in terms of pre-procedural characteristics. All-cause mortality at 5-year follow-up was similar in the 2 groups (6.4% for HCR vs. 9.2% for CABG; p = 0.69). The rates of myocardial infarction (4.3% vs. 7.2%; p = 0.30), repeat revascularization (37.2% vs. 45.4%; p = 0.38), stroke (2.1% vs. 4.1%; p = 0.35), and major adverse cardiac and cerebrovascular events (45.2% vs. 53.4%; p = 0.39) were also similar in the 2 groups., Conclusions: HCR has similar 5-year all-cause mortality when compared with conventional coronary bypass grafting (Safety and Efficacy Study of Hybrid Revascularization in Multivessel Coronary Artery Disease; NCT01035567)., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: This observational analysis investigated in-hospital safety and efficacy of periprocedural antithrombotic/antiplatelet therapy used in TAVI patients included into the Polish Nationwide Cardiac Surgical and Cardiology Registry of Transcatheter Aortic Valve Implantation (POL-TAVI)., Methods and Results: All patients who underwent TAVI in the participating centers between 2013 and 2014 were included. The primary endpoints were: severe bleeding, vascular complications, thromboembolic events, myocardial infarction, 30-days mortality, defined according to Valve Academic Research Consortium scale 2. A total of 827 patients were included; 35-93years old (79.31±7.53); 457 (55.29%) women. Endpoints noted: severe bleeding - 130 (15.72%) pts, vascular complications - 135 (16.32%) pts, thromboembolic events - 29 (3.5%) pts, myocardial infarction - 24 (2.90%) pts, deaths - 58 (7.01%) pts. Aspirin premedication, resulted in the least number of vascular complications (OR 0.56 95%CI [0.345-0.938]; p=0.027). Aspirin after TAVI reduced the risk of vascular complications (OR 0.089 95%CI [0.0217-0.372]; p=0.001) and bleeding (OR 0.138 95%CI [0.043-0.447]; p=0.001) with no adverse impact on efficacy endpoints. Beneficial safety profile of postprocedural aspirin monotherapy remained significant in comparison to all other types of prophylaxis also in propensity score analysis: OR 0.068 95%CI [0.009-0.529]; p=0.01 for vascular complications, OR 0.176 95%CI [0.049-0.627]; p=0.007 for bleeding. NNT for vascular complications and bleeding with postprocedural aspirin prophylaxis was 5.5 and 6.42, respectively., Conclusion: Aspirin after TAVI appears to be beneficial than currently recommended dual antiplatelet therapy; therefore, it might be considered as TAVI antithrombotic prophylaxis., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Tumor-derived microvesicles (TMV) can mimic effects of tumor cells leading to an increased anti-inflammatory cytokine production, such as interleukin 10 (IL-10), by tumor-infiltrating monocytes and macrophages. Yet, the mechanism of IL-10 induction by TMV in monocytes remains unclear. The co-incubation of TMV derived from the human pancreas carcinoma cell line (HPC-4) with human monocytes resulted in a nearly 30-fold increase in IL-10 protein production. This effect operates at the level of transcription since monocytes transduced with an adenovirus containing IL-10-promoter luciferase reporter gene showed a 5-fold induction of luciferase activity after treatment with TMV. Since tumor cells can express hyaluronan (HA), which participates in tumor invasion and metastases, we have tested its effect on IL-10 expression. We showed that HA at the concentration of 100μg/ml induces IL-10 protein expression and the IL-10 promoter activation in monocytes. Moreover, hyaluronidase treatment of TMV reduced IL-10 protein production by 50% and promoter activity by 40%. Inhibitors of the PI3K/Akt/mTOR pathway reduced both, TMV-induced IL-10 promoter activity and protein production, and the same was observed in monocytes when stimulated by HPC-4 cells or HA. Inhibition of PI3K activity down-regulated phosphorylation of the Akt and (to a lesser extent) mTOR proteins in monocytes following TMV or HA stimulation. When comparing monocyte subsets, TMV induced IL-10 protein and mRNA synthesis only in classical CD14 ++ CD16 - but not in CD16-positive monocytes. Our data show that TMV induce IL-10 synthesis in human classical monocytes via HA, which, in turn, activates the PI3K/Akt/mTOR pathway., (Copyright © 2015 Elsevier GmbH. All rights reserved.)

Background: Despite the popularity of less invasive approaches for conduits procurement in coronary artery bypass graft surgery, concerns have been raised about the potential detrimental effects of the endoscopic technique when compared with the conventional "open" technique., Methods: Among 470 patients undergoing coronary surgery with the use of a radial artery conduit, a propensity score analysis was performed among those patients assigned either to an open technique (n = 82) or to an endoscopic approach (n = 82). Endoscopic harvesting was performed with a nonsealed system. The primary endpoint was cardiac-related mortality, and secondary endpoint was survival free from major cardiac and cerebrovascular adverse events. Moreover, hand and forearm sensory discomfort and forearm wound healing were also assessed., Results: No conversion to the open technique occurred in patients undergoing endoscopic harvesting. No patients in either group showed hand ischemia; wound infection occurred only in the open group (open 7.3% versus endoscopic 0%, p = 0.007). Wound healing (Hollander scale) was considerably better in the endoscopic group (open 3.3, endoscopic 4.7; p < 0.001) as well as paresthesia at the latest follow-up (open 19.5% versus endoscopic 3.6%, p < 0.001). Pain (visual analog scale score) was significantly reduced with the endoscopic technique (open 3.2, endoscopic 1.2; p = 0.003). At 5 years of follow-up, freedom from cardiac-related mortality (open 96.3% ± 2.1% versus endoscopic 98.1% ± 1.8%; p = 0.448) as well as survival free from major cardiac and cerebrovascular adverse events (open 93.9% ± 2.6% versus endoscopic 93% ± 3.4%; p = 0.996) were similar among the groups., Conclusions: Endoscopic radial artery harvesting allows for incremental benefits in the short term in terms of improved cosmesis and reduced wound and neurologic complications, without yielding detrimental effects in terms of graft-related events at 5 years of follow-up., (Copyright © 2016 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Primary malignant cardiac tumors are rare, and mostly manifest as sarcomas in various types. As non-invasive diagnostic modalities, e.g. echocardiography and magnetic resonance imaging, have become more sensitive, there is a marked increase in the number of patients diagnosed. Nevertheless, most patients die within one year of initial diagnosis, either because of the often asymptomatic presentation of cardiac tumors until advanced disease, or a low index of suspicion on the part of the physician. The presenting symptoms, treatment options and, indeed, prognosis are largely controlled by the tumor's anatomic location. Cardiac sarcomas may present with a variety of symptoms and are known to be great mimickers. A quick diagnosis facilitates the initiation of a proper treatment (surgical resection, adjuvant chemotherapy), which may in turn improve the prognosis. Metastases to the heart are far more common, unfortunately, clinical manifestations are mainly dominated by generalized tumor spread. The article summarizes epidemiology, symptoms, diagnostic modalities, and possible treatment options., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: There is great variability for the type of anaesthesia used during TAVI, with no clear consensus coming from comparative studies or guidelines. We sought to detect regional differences in the anaesthetic management of patients undergoing transcatheter aortic valve implantation (TAVI) in Europe and to evaluate the relationship between type of anaesthesia and in-hospital and 1 year outcome., Methods: Between January 2011 and May 2012 the Sentinel European TAVI Pilot Registry enrolled 2807 patients treated via a transfemoral approach using either local (LA-group, 1095 patients, 39%) or general anaesthesia (GA-group, 1712 patients, 61%)., Results: A wide variation in LA use was evident amongst the 10 participating countries. The use of LA has increased over time (from a mean of 37.5% of procedures in the first year, to 57% in last 6 months, p<0.01). MI, major stroke as well as in-hospital death rate (7.0% LA vs 5.3% GA, p=0.053) had a similar incidence between groups, confirmed in multivariate regression analysis after adjusting for confounders. Dividing our population in tertiles according to the Log-EuroSCORE we found similar mortality under LA, whilst mortality was higher in the highest risk tertile under GA. Survival at 1 year, compared by Kaplan-Meier analysis, was similar between groups (log-rank: p=0.1505)., Conclusions: Selection of anaesthesia appears to be more influenced by national practice and operator preference than patient characteristics. In the absence of an observed difference in outcomes for either approach, there is no compelling argument to suggest that operators and centres should change their anaesthetic practice., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Objectives: The aim of this study was to assess the feasibility of hybrid coronary revascularization (HCR) in patients with multivessel coronary artery disease (MVCAD) referred for standard coronary artery bypass grafting (CABG)., Background: Conventional CABG is still the treatment of choice in patients with MVCAD. However, the limitations of standard CABG and the unsatisfactory long-term patency of saphenous grafts are commonly known., Methods: A total of 200 patients with MVCAD involving the left anterior descending artery (LAD) and a critical (>70%) lesion in at least 1 major epicardial vessel (except the LAD) amenable to both PCI and CABG and referred for conventional surgical revascularization were randomly assigned to undergo HCR or CABG (in a 1:1 ratio). The primary endpoint was the evaluation of the safety of HCR. The feasibility was defined by the percent of patients with a complete HCR procedure and the percent of patients with conversions to standard CABG. The occurrence of major adverse cardiac events such as death, myocardial infarction, stroke, repeated revascularization, and major bleeding within the 12-month period after randomization was also assessed., Results: Most of the pre-procedural characteristics were similar in the 2 groups. Of the patients in the hybrid group, 93.9% had complete HCR and 6.1% patients were converted to standard CABG. At 12 months, the rates of death (2.0% vs. 2.9 %, p = NS), myocardial infarction (6.1% vs. 3.9%, p = NS), major bleeding (2% vs. 2%, p = NS), and repeat revascularization (2% vs. 0%, p = NS) were similar in the 2 groups. In both groups, no cerebrovascular incidents were observed., Conclusions: HCR is feasible in select patients with MVCAD referred for conventional CABG. (Safety and Efficacy Study of Hybrid Revascularization in Multivessel Coronary Artery Disease [POL-MIDES]; NCT01035567)., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Even though coronary angiography (CAG) underestimates coronary allograft vasculopathy (CAV) development, especially in the distal parts of arteries, it remains a frame of reference for International Society for Heart and Lung Transplantation (ISHLT) CAV classification. A retrospective analysis was performed to assess the prognostic value of CAG findings., Methods: Among 310 orthotopic heart transplantation (OHT) recipients with at least 2 CAGs at 2-year intervals, we identified 197 (146 men and 41 women; 55 ± 13 years) without lesions (Group 0), 27 (15 men and 12 women; 58 ± 8 years) in whom mild changes remained in consecutive CAGs (Group 1), 28 (24 men and 4 women; 58 ± 10 years) in whom mild lesions decreased in consecutive CAGs (Group 1REG), and 58 (53 men and 5 women; 56 ± 10 years) in whom the stenosis criteria of ISHLT CAV 2 or 3 were covered (Group 2). We compared survival and other clinical variables among the groups., Results: The average follow-up was 10 ± 4 years. Forty-one (21%) deaths occurred in Group 0, 15 (56%) in Group 1 (p = 0.002), 9(31%) in Group 1REG (p = NS), and 26 (46%) in Group 2 (p = 0.004, chi-square test). Time free from all-cause death was significantly shorter in Group 1 (T1/2 = 8 years) than in Group 0 (T1/2 = 15.5 years; p = 0.00072, log-rank test). Time free from cardiovascular death was significantly shorter in Groups 1 and 2, as was time free from CAV-related death in Groups 1, 1REG, and 2. Multivariate analysis, using a Cox proportional hazards model, revealed that Group 1 inclusion criterion of CAG findings is an independent predictor of all-cause death, cardiovascular death, and CAV-related death., Conclusions: Persistent mild coronary lesions, observed in consecutive CAG, predicted shorter survival of OHT recipients., (© 2013 International Society for Heart and Lung Transplantation Published by International Society for the Heart and Lung Transplantation All rights reserved.)

Background: Mortality of patients with ST-segment elevation myocardial infarction (STEMI) with cardiogenic shock (CS) on admission remains high despite invasive treatment. The aim of this analysis was to assess the relationship between the infarct-related artery (IRA) and the early and 12-month outcomes of patients with STEMI and CS treated by percutaneous coronary intervention (PCI)., Methods: Two thousand ninety patients with STEMI and CS registered in the prospective Polish Registry of Acute Coronary Syndromes from October 2003 to November 2009 were included., Results: The in-hospital mortality in the left main (LM), left anterior descending artery (LAD), circumflex artery (Cx), and right coronary artery (RCA) groups was 64.7%, 41.0%, 36.0%, and 30.8%, respectively, with p<0.0001. The 12-month mortality in the LM, LAD, Cx, and RCA groups was 77.7%, 58.2%, 55.1%, and 45.0%, respectively, with p<0.0001. After multivariate adjustment, LM as the IRA was significantly associated with higher 12-month mortality (hazard ratio=1.71, 95% confidence interval=1.28-2.27, p=0.0002)., Conclusions: In-hospital and long-term mortality of patients with STEMI and CS treated by PCI are significantly correlated to the IRA, being highest for LM and lowest for RCA., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Background: Several patients with acute coronary syndrome (ACS) are discharged home after the acute phase of ACS and are suitable for elective coronary artery bypass graft (CABG) surgery. The aim of the study was to assess the optimal timing for surgical revascularization and its effect on 12-month outcome in patients discharged from hospital after ACS and referred for elective CABG surgery., Methods: The analysis involved 2028 patients enrolled into the ongoing Polish Registry of Acute Coronary Syndromes (PL-ACS) who were discharged from hospital with the intention to undergo elective CABG surgery., Conclusions: Among 2028 patients 1216 (60.0%) underwent surgery during 12months of follow-up. Patients who underwent surgical revascularization had a lower prevalence of mortality (5.7% vs 11.5%, p<0.0001). Patients who underwent surgery within the first month had a significantly higher prevalence of mortality than those who did not undergo surgery (5.7% vs 1.6%, p<0.0001). By the third month, the two cumulative mortalities were similar (4.2% vs 4.6%, p=0.65). From the beginning of the fourth month, the cumulative mortality was significantly higher among patients who did not undergo surgery., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Background: Prognoses in STEMI and NSTEMI beyond one year from onset remain unclear. We aimed to compare the treatments and the two-year outcomes in patients with myocardial infarction (MI) enrolled at the Polish Registry of Acute Coronary Syndromes (PL-ACS)., Methods: A total of 13,441 patients with MI (8250 with STEMI, and 5191 with NSTEMI) underwent medical care between October 2003 and June 2005 in the Silesia region (4.8 million inhabitants). The events analyzed were death, MI, stroke and percutaneous (PCI) or surgical (CABG) revascularization., Results: After two years, NSTEMI was associated with a higher incidence of death (hazard ratio (HR) of 1.09 (95% confidence interval (CI) 1.02-1.17, p<0.0001)); a higher incidence of reinfarction, stroke, CABG and a lower rate of PCI. Adjustments for baseline characteristics and treatment strategy (invasive vs. non-invasive) reversed the HR for mortality and eliminated the difference in MI and stroke. The adjusted HR for mortality was 0.76 (95% CI, 0.71-0.83, p<0.0001). STEMI and NSTEMI patients treated non-invasively were older and showed higher incidences of diabetes, obesity, pulmonary edema and cardiogenic shock than their invasively treated counterparts. Invasively treated patients received aspirin, beta-blockers, ACE inhibitors and statins more often during hospitalization and at discharge., Conclusions: The unadjusted long-term prognosis was worse in NSTEMI. After adjustment for the baseline characteristics and treatment strategy, the long-term prognosis was worse in STEMI. Patients with MI treated invasively showed more favorable clinical characteristics and received guideline-recommended therapy more often than patients who did not undergo invasive treatment., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Background: Disturbed glucose metabolism, particularly in diabetes, is an important but not the sole factor leading to advanced glycation end-product (AGE) formation. The AGE amount and its distribution in cardiopathic myocardial tissues in the presence or absence of diabetes are not well documented. The aim of this study was to assess AGE deposition in unaffected myocardial vessels in heart failure patients with and without diabetes mellitus type 2 (DM2) undergoing transplantation., Methods: The following groups were established: 14 hearts harvested from subjects with ischemic cardiopathy and DM2; 8 hearts from subjects with dilated cardiopathy with DM2; 67 hearts from subjects with ischemic cardiopathy; 47 hearts from subjects with dilated cardiopathy; and 14 hearts from autopsy cases with diagnosed DM2. A control group consisted of 20 heart donors. AGE localization was determined immunohistochemically in tissue sections. A semi-quantitative scale was used to assess reaction intensity in arteries, arterioles, capillaries, venules and veins., Results: Both types of cardiomyopathy increased AGE accumulation in intramyocardial veins more than in arteries. The presence of DM2 significantly increased AGE in arterioles and capillaries, especially when coexisting with cardiomyopathy. The type of cardiopathy did not influence the pattern of AGE accumulation in myocardial vessels., Conclusion: Both chronic heart failure and DM2 intensified AGE pathology and changed the susceptibility of myocardial vasculature to glycation. However, chronic heart failure increases AGE deposition mostly in veins, whereas DM2 predisposes arterioles to AGE accumulation., (Copyright © 2011 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Several in vivo and in vitro studies have shown that metal-rich particles may enhance allergic responses to house dust mites and induce an increased release of allergy-related cytokines., Objectives: The main goal of this analysis is to define the possible association of intrauterine exposure to lead and mercury with the occurrence of skin sensitization to common aeroallergens in early childhood., Material and Methods: The present study refers to a sample of 224 women in the second trimester of pregnancy recruited from Krakow inner city area who had full term pregnancies and whose children underwent skin prick testing (SPT) at the age of 5. Lead and mercury levels were assessed in cord blood and retested in children at age of 5 years. Aeroallergen concentrations in house dust were measured at the age of 3 years. The main health outcome (atopic status) was defined as the positive SPT to at least one common aeroallergen (Der f1, Der p1, Can f1 and Fel d1) at the age of 5 years. In the statistical analysis of the association between atopic status of children and exposure to metals, the study considered a set of covariates such as maternal characteristics (age, education, atopy), child's gender, number of older siblings, prenatal (measured via cord blood cotinine) and postnatal environmental tobacco smoke together with exposure to polycyclic aromatic hydrocarbons (PAH) as measured by PAH-DNA adducts., Results and Conclusion: In the binary regression analysis, which controlled for the confounders, the risk ratio (RR) estimate for atopic sensitization was significantly associated with the lead exposure (RR=2.25, 95%CI: 1.21-4.19). In conclusion, the data suggest that even very low-level of prenatal lead exposure may be implicated in enhancing sensitization to common aeroallergens in early childhood., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Monocytes and cells of the dendritic cell lineage circulate in blood and eventually migrate into tissue where they further mature and serve various functions, most notably in immune defense. Over recent years these cells have been characterized in detail with the use of cell surface markers and flow cytometry, and subpopulations have been described. The present document proposes a nomenclature for these cells and defines 3 types of monocytes (classical, intermediate, and nonclassical monocytes) and 3 types of dendritic cells (plasmacytoid and 2 types of myeloid dendritic cells) in human and in mouse blood. This classification has been approved by the Nomenclature Committee of the International Union of Immunological Societies, and we are convinced that it will facilitate communication among experts and in the wider scientific community.

In some types of cancers, tumour-infiltrating monocytes/macrophages (TIM) may be responsible for the formation of an invasive microenvironment in a manner dependent on the secretion of soluble mediators such as tumour necrosis factor-alpha (TNF). Human pancreatic carcinoma (HPC-4) cells are able to induce TNF production by monocytes. Here, the effect of human peripheral blood monocytes, precursors of TIM, on the motility of co-cultured HPC-4 cells, was directly analysed in vitro. A phenotypic transition, i.e., the appearance of rear-front polarised HPC-4 cells paralleled by their increased motility, and increased motility of monocytes, were observed. This effect was attenuated when HPC-4 cells and monocytes were co-cultured in the presence of inhibitors of TNF production and anti-TNF monoclonal antibodies, indicating the specific role of this cytokine in determining paracrine loops between monocytes and cancer cells. Moreover, exogenous TNF induced HPC-4 cell motility concomitantly to the appearance of cellular features characteristic for epithelial-mesenchymal transition (EMT) such as rear-front polarisation, rearrangements of the actin cytoskeleton characteristic for motile cells and the induction of Snail-1 expression. Since cell movement is crucial for cancer invasion and the formation of metastases, these findings demonstrate an EMT-dependent mechanism of cancer progression which acts through the phenotypic transition of pancreatic cancer cells dependent on monocyte-derived TNF.

Background: Perioperative hyperglycemia should be avoided in patients undergoing coronary surgery. The aim of our study was to find out what the influence of cardiopulmonary bypass is on postoperative glycemia and insulin consumption in patients with and without diabetes mellitus undergoing coronary artery surgery and whether a marked hyperglycemia in the early postoperative period is among the factors associated with early mortality and morbidity., Methods: We retrospectively reviewed all patients who underwent first-time coronary artery surgery in our institution during the 11-month period. Among 814 patients, 239 patients (29.4%) had diabetes and 575 patients (70.6%) were nondiabetic. Blood glucose levels were registered every 2 hours in all patients during the first 24 postoperative hours. Outcomes were difficult glycemic control (postoperative blood glucose levels >11.0 mmol/L despite aggressive insulin treatment), hospital mortality, and morbidity (defined as any postoperative complication such as stroke, renal failure, wound infection, perioperative myocardial infarction, ventilation > 24 hours, sepsis, and multiorgan failure)., Results: Glycemic control was significantly worse in patients who underwent coronary artery bypass grafting, in comparison with off-pump coronary artery bypass grafting surgery, particularly in nondiabetic patients. Patients with difficult glycemic control had more serious postoperative complications resulting in higher mortality (2.5% versus 0.4%; p = 0.02). In the multivariate analysis, difficult glycemic control was significantly associated with a female sex (odds ratio [OR], 2.36), presence of diabetes (OR, 2.22), and the usage of cardiopulmonary bypass (OR, 1.81). Mortality was significantly associated with the left ventricular ejection fraction less than 0.35 (OR, 7.38), difficult glycemic control (OR, 7.06), and previous stroke (OR, 5.66). Difficult glycemic control was also significantly associated with postoperative morbidity (OR, 1.87)., Conclusions: Cardiopulmonary bypass increases postoperative glycemia and insulin consumption in both diabetic and nondiabetic patients. The use of cardiopulmonary bypass during coronary artery surgery in diabetic women is associated with a more difficult glycemic control in the early postoperative period. Difficult glycemic control is significantly associated with early mortality and morbidity in patients undergoing coronary artery surgery.

Background: Application of a tissue-engineered vascular graft for small-diameter vascular reconstruction has been a long awaited and much anticipated advance for vascular surgery. We report results after a minimum of 6 months of follow-up for the first ten patients implanted with a completely biological and autologous tissue-engineered vascular graft., Methods: Ten patients with end-stage renal disease who had been receiving haemodialysis through an access graft that had a high probability of failure, and had had at least one previous access failure, were enrolled from centres in Argentina and Poland between September, 2004, and April, 2007. Completely autologous tissue-engineered vascular grafts were grown in culture supplemented with bovine serum, implanted as arteriovenous shunts, and assessed for both mechanical stability during the safety phase (0-3 months) and effectiveness after haemodialysis was started., Findings: Three grafts failed within the safety phase, which is consistent with failure rates expected for this high-risk patient population. One patient was withdrawn from the study because of severe gastrointestinal bleeding shortly before implantation, and another died of unrelated causes during the safety period with a patent graft. The remaining five patients had grafts functioning for haemodialysis 6-20 months after implantation, and a total of 68 patient-months of patency. In these five patients, only one intervention (surgical correction) was needed to maintain secondary patency. Overall, primary patency was maintained in seven (78%) of the remaining nine patients 1 month after implantation and five (60%) of the remaining eight patients 6 months after implantation., Interpretation: Our proportion of primary patency in this high-risk cohort approaches Dialysis Outcomes Quality Initiative objectives (76% of patients 3 months after implantation) for arteriovenous fistulas, averaged across all patient populations.

Background: The appropriate therapy after orthotopic heart transplantation (OHT) is determined by the results of endomyocardial biopsies (EMBs). The Quilty effect (QE) is a recognized cause of discrepancies in EMB grading, but its clinical implications remain unclear. In this study we assess the correlation of the QE with biopsy-proven acute cellular rejection (AR) and coronary artery vasculopathy (CAV)., Methods: We reassessed 5,361 EMB samples, obtained from 429 patients, based on QE occurrence and its impact on EMB score. Next, we divided all patients with at least 1 year of follow-up into two groups: a QE(+) group (n = 202, 58.7% of sample, 172 males/30 females, 44.8 +/- 12 years of age) and a QE(-) group (n = 142, 41.3% of sample, 124 males/18 females, 45.4 +/- 12 years of age), and compared AR and CAV occurrences., Results: The QE was observed in 669 EMBs (12.5%), and at least 1 EMB with QE was found among the 231 patients (53.8%). The initial QE occurrence took place during the first 3 months after OHT in 68% of QE(+) patients, and >1 year post-OHT in 13% of patients. The average EMB score was significantly higher in QE(+) biopsies. A comparison of the two groups revealed a significantly higher number of AR episodes and number of patients with at least one episode of AR in QE(+) patients. There was no significant difference in number of CAV occurrences between groups., Conclusions: The QE seems to be a marker of the same increased immune system activity that can lead to AR. A relationship between QE and CAV was not supported by the present results.

Cardiac operations may be performed in a conscious, spontaneously breathing patient, but it is difficult to justify an awake technique in patients undergoing coronary artery procedures with low operative risk. We describe an elderly patient with severe chronic obstructive pulmonary disease in whom general anesthesia was contraindicated. A valve procedure was performed under thoracic epidural anesthesia alone, thus avoiding intubation and mechanical ventilation. The patient had an uneventful postoperative course and excellent recovery.

Unlabelled: sCD30 and ICE/caspase-1 as apoptosis-regulating factors are suspected to be involved in the survival rate of immunocompetent cells during immunosuppression after allotransplantation. Serum CD30 and ICE/caspase-1 concentrations were estimated and associated with unspecific serum apoptosis marker--anti-Annexin V antibodies and myocardial biopsies results., Materials and Methods: 28 clinically stabile patients--heart transplant recipients at least 3 months after cardiac transplantation performed due to heart failure caused by ischaemic and/or congestive cardiomyopathy or/and primary valvular heart disease (26 men and 2 women, mean age=36.8 years, S.D.=7.6) with normal heart function assessed by use of ultrasound scan--were involved in the trial. The patients were divided and analyzed in two ways: first according to the results of elective endomyocardial biopsies and second to main immunosuppressive agent used. The enzyme immunoassay (CD30, Dako; interleukin-1beta-converting enzyme (ICE)/Caspase-1 ELISA and anti-Annexin V BENDER MedSystem) for soluble CD30, caspase-1 and anti-Annexin V autoantibodies serum levels was used., Results: sCD30 and caspase-1 concentrations were non-significantly up-regulated in all analysed groups--with or without rejection signs or immunosuppressed with cyclosporine or especially tacrolimus. In contrast anti-Annexin V autoantibodies concentration was non-significantly down-regulated also in all studied groups. Moreover in the group with signs of transplant rejection, strong negative correlation between anti-Annexin antibodies and rejection grade was observed (-0.65, p<0.05). Biopsy results were comparable in groups treated with tacrolimus and cyclosporine A., Conclusions: The increasing tendency of sCD30 and caspase-1 as well as the decrease in anti-Annexin V autoantibodies concentrations in heart recipients could be the result of post-transplant apoptosis disturbances. This tendency seems to be inhibited in a greater degree by tacrolimus than by cyclosporine. Anti-Annexin V autoantibodies might be considered as negative rejection markers due to their strong negative correlation with the rejection grade.

Methods of theoretical and experimental evaluation of irreversible adsorption of particles, e.g., colloids and globular proteins at heterogeneous surfaces were reviewed. The theoretical models were based on the generalized random sequential adsorption (RSA) approach. Within the scope of these models, localized adsorption of particles occurring as a result of short-ranged attractive interactions with discrete adsorption sites was analyzed. Monte-Carlo type simulations performed according to this model enabled one to determine the initial flux, adsorption kinetics, jamming coverage and the structure of the particle monolayer as a function of the site coverage and the particle/site size ratio, denoted by lambda. It was revealed that the initial flux increased significantly with the site coverage theta(s) and the lambda parameter. This behavior was quantitatively interpreted in terms of the scaled particle theory. It also was demonstrated that particle adsorption kinetics and the jamming coverage increased significantly, at fixed site coverage, when the lambda parameter increased. Practically, for alpha = lambda2theta(s) > 1 the jamming coverage at the heterogeneous surfaces attained the value pertinent to continuous surfaces. The results obtained prove unequivocally that spherically shaped sites were more efficient in binding particles in comparison with disk-shaped sites. It also was predicted that for particle size ratio lambda < 4 the site multiplicity effect plays a dominant role, affecting significantly the structure of particle monolayers and the jamming coverage. Experimental results validating main aspects of these theoretical predictions also have been reviewed. These results were derived by using monodisperse latex particles adsorbing on substrates produced by covering uniform surface by adsorption sites of a desired size, coverage and surface charge. Particle deposition occurred under diffusion-controlled transport conditions and their coverage was evaluated by direct particle counting using the optical and electron microscopy. Adsorption kinetics was quantitatively interpreted in terms of numerical solutions of the governing diffusion equation with the non-linear boundary condition derived from Monte-Carlo simulations. It was proven that for site coverage as low as a few percent the initial flux at heterogeneous surfaces attained the maximum value pertinent to homogeneous surfaces. It also was demonstrated that the structure of larger particle monolayers, characterized in terms of the pair correlation function, showed much more short-range ordering than predicted for homogeneous surface monolayers at the same coverage. The last part of this review was devoted to detection of polyelectrolyte multilayers on various substrates via particle deposition experiments.

The present article contains a brief biography as well as a discussion of the more significant contributions of Albert Wojciech Adamkiewicz, Head of General and Experimental Pathology at the Jagiellonian University in Cracow in the years 1879 to 1892, and who is now primarily remembered as the discoverer of the major radicular artery eponymically named "Adamkiewicz's artery." His work as an investigator of the variability of the vasculature of the spinal cord led to his major contributions to present clinical practice in such areas as vascular surgery, neurosurgery, pediatric surgery, and the surgery of the aorta, providing a permanent Polish eponymic accent in major textbooks in these specialties. This article also deals with Adamkiewicz's contributions in other fields, mostly involving the nervous system, such as the development of a new and original method for staining neuronal tissue (double staining of the spinal cord) and his extensive studies of spinal cord degeneration. The authors also present aspects of his career that brought ill fame to Adamkiewicz. These were his claims to have discovered the so-called nervous bodies and anticancer antitoxin, which were both severely criticized by his faculty peers at the Jagiellonian University. The biography is supplemented with an attempt at evaluating Adamkiewicz's entire scientific output, wherein unquestionable achievements and pointed discoveries prevail in comparison with failures.

Background: Hepatocyte growth factor (HGF) is a member of growth factor with a variety of known activities, including angiogenesis promotion and antiapoptotic action. It prevents acute graft-versus-host disease after bone marrow transplantation and prolongs allogenic graft survival in rats. The aim of the study was to investigate the relationship between serum HGF concentration and the grade of acute cellular rejection of heart transplant., Methods: We studied 68 male heart recipients. All of them received triple-drug immunosuppression: cyclosporine A, prednisone, and azathioprine or mycofenolate mofetil. All patients were without signs of heart failure. Blood samples were taken before elective ambulatory endomyocardial biopsy. Biopsy specimens were graded with the International Society for Heart and Lung Transplantation scale. Acute cellular rejection grade 3A and higher were considered as significant. Measurement of serum HGF was made by enzyme-linked immunosorbent assay., Results: We found a positive relationship between serum HGF levels and grade of cellular rejection. As an indicator for the detection of cell rejection processes, HGF with cutoff 2000 pg/ml seems to be useful., Conclusions: The results of this study demonstrate that HGF can be useful as an indicator for heart graft cell rejection.

The influence of surface heterogeneity of various types on electrokinetic parameters is reviewed. The scope of the paper covers classical electrokinetic phenomena characterized by linear dependence of electrokinetic parameters vs. related driving forces. Neither non-linear effects nor the effects of non-equilibrium electric double layer are considered. A historical description of hydrodynamic aspect of electrokinetic phenomena exploiting the slip plane idea is briefly outlined. Attempts to estimate the slip plane location by comparing the diffuse layer and zeta potential values for some model systems are presented. The surface heterogeneity was divided into three categories. Heterogeneity of the first type was related to geometrical morphology of an interfacial region characterized by a considerable surface development producing a three-dimensional interfacial region. The effects of solid roughness, hairy surface, dense polymer layers and gel-like layers are discussed here. The very high surface conductivity detected for such interfaces seems to be a good indicator of the presence of structured layers of this type. Heterogeneous interfaces of the second class cover systems exhibiting non-uniform distribution of surface charge. The non-uniform surface charge distribution can be either of a molecular (discrete charges) or of a microscale (two-dimensional micropatches or three-dimensional structures formed by polyelectrolyte multilayers). The last class of systems examined includes interfaces composed of charged substrate covered by charged bulky objects (particles). In comparison to the homogeneous surfaces, adsorbed charged particles modify both hydrodynamic flow and the electrostatic field significantly altering the electrokinetic parameters. The new description of electrokinetics of composed interfaces presented here takes into account both hydrodynamic and electric field modification and is free of the previously assumed slip plane shift caused by adsorbed objects. This theoretical approach verified by experiments performed on well defined model systems can be successfully applied to the interpretation of experimental data obtained for surfaces covered by objects difficult to detect.

Recent studies demonstrate that activation of proinflammatory cytokines following injury intensifies the process of nociception. The present investigation assessed the influence of pre-injury pentoxifiline (PTFL, a non-specific cytokine inhibitor) on the development of post-injury nociception in animals and patients. It was established that intrathecal or intraperitoneal PTFL, elevated the nociceptive threshold for mechanical stimuli in the formalin test in rats. Pre-injury PTFL also inhibited pain-related behaviour. These findings correlate with a lower TNFalpha level in the serum of animals receiving pre-injury PTFL. In clinical investigations PTFL was administered intravenously before elective cholecystectomy. Patients who received preoperative PTFL had lower opioid requirements in the early postoperative period than control. At the same time, serum levels of TNFalpha and IL6 were lower in the PTFL group. Our results confirm the hypothesis as to the possibility of modulating of nociception through preemptive administration of a cytokine inhibitor.

Study Objective: To determine if treatment with inhaled budesonide forte can diminish increased bronchial hyperreactivity and improve symptoms in patients with mitral valve stenosis., Design: The study was randomized, double blind, and placebo controlled., Setting: Outpatient/university hospital., Patients: Twelve subjects, 8 female and 4 male, who qualified for mitral valve replacement. All subjects presented with increased bronchial reactivity to histamine at the time of the study., Interventions: Patients received placebo or budesonide forte twice a day (1,200 mg/d) for 6 weeks. During the study, patients were treated with the same doses of diuretics and other medications that could affect bronchial reactivity., Measurements: Spirometry, provocative concentration of histamine causing a 20% fall in the FEV1 (PC20H), symptom scores., Results: In the treated group, the initial PC20H was 0.82+/-0.72 mg/mL; in the placebo group 1.39+/-1.3 mg/mL. After 6 weeks of treatment, PC20H was significantly higher (3.07+/-2.28 mg/mL; p > 0.01) in the budesonide-treated group and remained unchanged in the placebo group (1.49+/-0.91). Symptom scores were significantly lower after administration of budesonide forte (mean change, 4.0+/-2.6)., Conclusions: Six weeks of treatment with budesonide forte significantly decreased bronchial reactivity to histamine and improved symptoms in patients with mitral valve stenosis.

Several phenotypic and functional changes of monocytes (M phi) have been described in HIV-1+ subjects and AIDS patients. Some of these changes that are pertinent for immunopathogenesis of the disease may be induced by HIV-1 envelope glycoprotein 120 (gp120). In the present study the effect of recombinant full length gp120 (FLgp120) and its two fragments: rp120cd (aa 410-511) and rp120 (aa 446-511) on the expression of the surface molecules of M phi cultured in vitro was determined. The FLgp120 and rp120cd caused upregulation of CD14 and CD44. The rp120cd peptide significantly increased the expression of CD16 (Fc gamma receptor type III) and TNF receptor type II. In contrast, the rp120 downregulated HLA-DR, CD64 (Fc gamma RI), interferon gamma receptor and induced IL-10 production by M phi. This study indicates that gp120 molecule and its fragments may induce several phenotypic changes of M phi in particular the increased proportion of CD14+CD16+ cells that is observed in the blood of AIDS patients. These results provide further evidence for variable response of M phi to gp120 which may explain the variability of phenotypic changes and heterogeneity of M phi subsets seen in HIV-1 disease.

Twelve male heart transplant recipients underwent routine electrophysiologic evaluation. None were taking cardioactive drugs, and only two had symptoms of arrhythmia. Two patients had endocardial VVI pacemakers because of previous early sinus node dysfunction. With simultaneous endomyocardial biopsy, we found seven patients with no evidence of rejection (group 1) and five patients with mild rejection (group 2; three initial or mild; two definite rejection). In two group 1 patients with presyncope, corrected sinus node recovery time was prolonged, and pacemakers were implanted into the endocardium. In all patients atrioventricular conduction was normal. One patient had evidence of functional duality of anterograde atrioventricular nodal conduction. In group 2 patients prolongation of effective refractory period of the donor atrium, functional refractory period of the atrioventricular node, and effective refractory period of the right ventricle were observed. This prolongation of refractoriness may be one of the earliest markers of rejection.

Monoclonal and conventional cryptococcal-specific T suppressor factors (TsF) (also called TsFmp) depress phagocytosis by a subset of macrophages, while picryl- and oxazolone-specific TsF depress the passive transfer of contact sensitivity. This paper shows that these haptene-specific TsF also inhibit phagocytosis by a subset of macrophages and, using this assay, that the anti-haptene TsF resemble the anti-cryptococcal TsF in five respects: (i) the need for reexposure to specific antigen to trigger the release of TsF; (ii) genetic restriction in action; (iii) possession of an antigen-binding site; (iv) expression of I-J determinants; and (v) inactivation by reduction and alkylation. Purification of the anti-picryl TsF by sequential affinity chromatography indicates that the inhibition of phagocytosis is due to the TsF itself and not to a TsF-antigen complex. The TsF inhibits phagocytosis by a direct action as macrophages treated with TsF and exposed to antigen do not release a second factor which inhibits phagocytosis. These results and those of the accompanying paper indicate that the anti-cryptococcal and anti-haptene TsF are functionally equivalent, antigen-specific suppressor factors.

Monoclonal anti-cryptococcal TsF (which inhibits phagocytosis by macrophages) and anti-picryl TsF use the same two circuits to block the transfer of contact sensitivity (CS). Both arm macrophages which then release a macrophage suppressor factor (MSF) when exposed to antigen. This MSF depresses the transfer of CS. The evidence suggests that a single molecular species of TsF (MW ca. 70 kDa), which bears an antigen-binding site and I-J determinant, is responsible for MSF production and inhibition of phagocytosis. Anti-cryptococcal TsF also arms the T acceptor cell which then releases nsTsF-1 after triggering with a specific antigen (SCPA). This nsTsF-1, which depresses the transfer of contact sensitivity, was authentic, as shown by its I-J positivity (in contrast to MSF) and its role in the production of nsTsF-2. As anti-picryl TsF also inhibits phagocytosis, it was concluded that anti-cryptococcal TsF, originally detected by the inhibition of phagocytosis, and anti-picryl TsF, originally detected by inhibition of CS, are functionally equivalent.

The production of a nonspecific inhibitor of DNA synthesis (nsINH) appears to be one of the final events in the T-suppressor cell circuit in mice exposed to contact sensitizers. We report here that: The nsINH suppresses the proliferative response to a polyclonal T-cell mitogen, concanavalin A (Con A), regardless of the dose of Con A used. It also suppresses DNA synthesis in lymphoid cells stimulated with alloantigens. This suppression can be completely eliminated by adding exogenous interleukin 2 (IL-2). DNA synthesis in lymphoid cells exposed to nsINH before the proliferative stimulus is uninfluenced so that activation of the lymphoid cells at the same time as exposure to nsINH seems to be a requirement for its action. Since the activity of nsINH can be absorbed by activated Lyt-1+ or Lyt-2+ lymphocytes, the early activated T cell appears to be a target of the action of nsINH. The production of nsINH is abolished or severely reduced by adult thymectomy. Natural killer (NK) cells are resistant to nsINH action and no interferon (IFN)-like activity can be demonstrated in nsINH preparation using a conventional assay for IFN.

Mice primed with picrylsulfonic acid (PSA) and then painted on the skin with picryl chloride produce antigen-specific T suppressor factor (TsF). In contrast unpainted primed mice fail to produce active TsF. This is not due to the absence of the antigen binding part of TsF but to the absence of a cofactor. This cofactor is (a) antigen nonspecific and occurs in potassium chloride extract of normal spleen cells. It also occurs in the 24 hr supernatant of normal cells modified by haptenisation with picryl or the unrelated NP antigen (4-hydroxy-3-nitrophenylacetyl), and in preparations of conventional TsF (PSA/PCl) from painted PSA-primed mice; (b) bears I-J determinants; and (c) is produced by Lyt-1+2(-)I-J+ cells. The antigen binding molecule occurs alone in the supernatant of PSA-primed mice. It lacks I-J determinants and has a molecular weight around 35,000 and 75,000. It is produced by Lyt-1(-)2+I-J+ cells and is only active when complemented by cofactor. However, the complementation is genetically restricted and the restriction maps to the I-J subregion of the MHC.

The phenomenon of associative recognition, i.e., the recognition of antigen together with major histocompatibility complex products (MHC) was studied in a model system. T-acceptor cells armed with antigen-specific T-suppressor factor (TsF) released a nonspecific inhibitor of the transfer of contact sensitivity when exposed to antigen together with MHC. The MHC product occurred in a KCl extract of cells and behaved genetically and serologically as I-J. Cells armed with anti-picryl or anti-"oxazolone" TsF could be triggered by the corresponding "bis-picryl-L-lysine" and "bis-oxazolone-L-lysine" together with MHC. This suggested that cross-linking of antigen recognition sites on separate molecules of TsF might be required. To investigate this possibility the bifunctional "mixed" hapten "N alpha-picryl-N epsilon-oxazolone-L-lysine," which is univalent with respect to the picryl and oxazolone haptenic groups, was synthesized. This triggered cells armed with a mixture of anti-picryl and anti-oxazolone TsF but not cells armed with either TsF alone. It was concluded that both occupancy of the I-J recognition site and the cross-linking of separate molecules of TsF was required for triggering. Moreover the hapten and the KCl extract could be given sequentially and in either order. This finding suggested that the triggering of the release of nonspecific inhibitor was due to the separate recognition of I-J and antigen and not to new antigenic determinants produced by their interaction.

Antigen-specific T-helper factor (ThF) augments the contact sensitivity reaction induced by the injection of small numbers of picrylated cells into mice. ThF was produced by injected picrylated spleen cells into the footpads and taking the 24-hr culture supernatant of the regional lymph node cells. Analysis showed that there was a genetic restriction in the induction of ThF, between these picrylated cells and the mouse making the ThF, which maps to the I-A region. This finding suggests that the receptor on the T cell which makes ThF, and by implication ThF itself, bears recognition site(s) for both antigen and I-A. ThF was then prepared from mice painted on the skin with picryl chloride, and the genetic restriction in its action was investigated. There was a requirement for genetic matching between the mouse producing the ThF and the final recipient which mapped to the I-A region. The genotype of the picrylated cell used as a source of antigen was unimportant. This I-A genetic restriction, together with the finding that ThF bears at least some I-A determinants, suggests that ThF may act by binding to the picrylated cells used as a source of antigen through its antigen-binding site and hence provide the I-A determinants needed for the recognition of antigen in the context of self-MHC. The present findings add to the list of antigen-specific factors which have a two-chain structure and show genetic restriction in their induction, action, and in the interaction between their chains which maps to the same region as the MHC-related determinant(s) which they bear.

The T suppressor efferent circuit in the picryl (TNP) system, which inhibits the passive transfer of contact sensitivity, involves at least two antigen-nonspecific factors. The second nonspecific T suppressor factor (ns-2) bears I-A determinants of both the alpha and the beta chain as shown by affinity chromatography on immobilized anti-I-A monoclonal antibodies. Sequential absorption shows that the determinants of the alpha and beta chain occur on the same molecular complex. No absorption was obtained with anti-I-E antibody. There are two genetic restrictions associated with ns-2--the first is in its release from the second T suppressor efferent cell (on exposure to antigen) and the second is in its inhibitory interaction with its target cell. Both are MHC restricted and matching in I-A (but not I-E, or I-J) is sufficient. The question was asked whether the I-A of the ns-2 was directly responsible for the I-A genetic restriction in its action. F1 TsF was made in (H-2k X H-2b)F1 mice by injecting picrylated parental cells intravenously and triggering the release of ns-2 with the corresponding picrylated parental cells. Both I-Ak- and I-Ab-positive ns-2 were produced and were separated by affinity chromatography on immobilized anti-I-A monoclonal antibody. The I-A phenotype of these separated ns-2 of F1 origin determines the genetic restriction in their action; i.e., I-Ak+ ns-2 only inhibits passive transfer by H-2k cells and I-Ab+ ns-2 only acts on H-2b cells. In contrast, the I-A haplotype of the picrylated cell used to induce the Ts cell which makes ns-2 is unimportant. It was concluded that the I-A on the ns-2, and not a possible recognition site for I-A, serves as a restriction element. This finding suggests that ns-2 may act directly on the I-A-restricted T cell which mediates contact sensitivity.

Mice injected with antigen (picrylated spleen cells) intravenously fail to develop contact sensitivity. However, contact sensitivity occurs if these mice are injected with IL-2. This effect of IL-2 was reproduced in vitro by taking spleen cells 2 days after injecting antigen intravenously and culturing them with either 150 u/ml recombinant IL-2 for 2 days or by pulsing with 600-1200 u/ml IL-2 at 4 degrees C for 1 hr. After 2 days in culture these antigen-exposed cells transfer contact sensitivity to naive recipients in a 24-hr experiment. However, the ability of antigen-exposed cells, pulsed with IL-2, to transfer contact sensitivity is abolished when they are incubated with unpulsed antigen-exposed cells and as few as 1/16 of their number have a significant effect. This phenomenon is specific, as normal cell or cells from mice injected with oxazolonated cells intravenously have no effect. The suppressor cells were Thy-1+, Lyt-1-, 2+, I-J+ T cells. It was concluded that IL-2 prevents the development/action of antigen-specific T suppressor cells.

The ability of human monocytes from normal donors and gastric-cancer patients to form rosettes with "O" Rh+(D) human erythrocytes coated with hyperimmune IgG anti-D antibody (EAhu) and to kill the same target in antibody-dependent cellular cytotoxicity (ADCC) were assessed. Trypsin pretreatment of normal monocytes decreased their ability to form rosettes with EAhu complexes, but their ADCC activity was unaffected. The Fc receptor (FcR) expression and ADCC activity of monocytes of cancer patients were elevated, and trypsin-treatment led to their further increase. The elevated values were related to the presence of the tumour. These results may suggest that human monocytes possess trypsin-sensitive and trypsin-resistant Fc receptors. The trypsin-resistant FcR seems to be involved in ADCC phenomenon and to be preferentially expressed on monocytes of some cancer patients.

Antigen-specific T-helper factor (ThF) of CBA (H-2k) origin in the picryl (TNP) contact sensitivity system (Mr 60-70 kDa) was reduced with dithiothreitol under mild conditions. Affinity chromatography on antigen yielded an antigen-binding chain (Mr 20-30 kDa) and an antigen-nonbinding chain (Mr 40-50 kDa). Both chains were glycoproteins and were bound by lentil lectin. Affinity chromatography on anti-I-A monoclonal antibodies showed that I-A determinants occurred on the complete molecule and on the antigen-nonbinding, but not on the antigen-binding, chain. In contrast, five different monoclonal antibodies to I-E alpha failed to absorb ThF. Moreover, the complete molecule and the I-A+ antigen-nonbinding chains had determinants of the alpha and beta chains of I-A and conformational determinants which are based on both chains. Sequential absorption and elution showed that A alpha and A beta determinants occurred on the same molecular complex. These data suggest a minimal model of ThF as a two-chain disulfide-bonded structure with an antigen-binding chain and a separate I-A+ antigen-nonbinding chain which behaves as a single unit in phosphate-buffered saline and has elements of both A alpha and A beta.

Antigen-specific T-suppressor factor (TsF), which acts at the expression stage of the contract sensitivity reaction, was produced by culturing the lymphoid cells of mice injected with picryl-sulphonic (trinitrobenzenesulphonic) acid and then painted with picryl chloride. Supernatant activity was found around 50-60 and 90 kDa on Sephadex gel filtration. The activity at 50-60 kDa was due to two separate (or readily separable) molecules, one antigen binding and the other bearing I-J determinants as shown by affinity chromatography on insolubilized antigen and anti-I-J. These two separate molecules were inactive alone but complemented each other and may be designated as the variable chain of TsF (TsFv) and the I-J+ chain. The use of gel filtration and sequential absorption of individual pools on anti-I-J antibody followed by antigen, together with a complementation assay, also showed a TSFv chain at 30-40 kDa and an I-J+ chain at 20-30 kDa. The higher-molecular-weight activity around 90 kDa was due to a single molecule which was both antigen binding and I-J+. This molecule dissociated on treatment with the reducing agent dithioerythritol followed by alkylation into two separate chains, one antigen binding and the other I-J+, both of which were required for activity. There was a requirement for genetic matching between the antigen-binding chain (TsFv) and the I-J+ chain for biological activity. These data support a two-chain model of TsF in which TsFv and the I-J+ chain occur as a single disulphide-bonded molecule around 90 kDa, or as two separate (or readily separable) chains of lower molecular weight which were inactive alone but complemented each other.