In this study, a B cell growth stimulatory factor, constitutively secreted by a human CD4+ T cell hybridoma clone, MP6, has been purified and characterized. Serum-free 24 h culture media from MP6 cells were collected, concentrated by ultrafiltration and separated by gel chromatography. Fractions were analyzed for stimulatory activity using [3H]thymidine incorporation in normal and leukemic (B-CLL) B cells as target cells. Activity was present in a 12 kDa protein peak. Upon storage this lost activity indicating that the factor was sensitive to air oxidation, a well-known property of mammalian thioredoxins (Trxs). Treatment of the inactive fraction with dithiothreitol restored full activity. When culture medium was analyzed with a radioimmunoassay for human placenta Trx, the MP6 clone was shown to release 30-50 ng/ml per million cells during 24 h. The B cell stimulatory activity of the MP6 medium was removed by Sepharose-bound anti-human placenta Trx IgG and activity was recovered by elution from the antibodies. Furthermore, MP6 medium showed Trx activity with NADPH and Trx reductase using an insulin disulfide reduction assay. Starting from 5 l of serum-free MP6 conditioned medium, the Trx was purified approximately 100,000-fold. After gel electrophoresis banding, the material was analyzed by peptide sequencing and a full length sequence of an 104 amino acid long protein was obtained. This Trx sequence was identical to the previously published sequence of human Trx from HTLV-1 transformed T cells, adult T cell leukemia-derived factor/Trx.(ABSTRACT TRUNCATED AT 250 WORDS)

Background Despite abundant knowledge about the relationship between inflammation and coronary artery disease (CAD), it is still unknown whether high sensitivity C-reactive protein (hsCRP) is associated with coronary atherosclerosis in the general population. Objectives The project aimed to study the association between systemic inflammation, measured as hsCRP, and coronary artery atherosclerosis in a large population based cohort. Methods 30,154 randomly selected men and women aged between 50 and 64 years were included in the SCAPIS (Swedish Cardiopulmonary Bioimage Study). After excluding those not undergoing coronary computed tomography angiography (CCTA), those with proximal segments not technically assessable and those with missing values of hsCRP, 25,408 individuals were analysed. Coronary artery atherosclerosis was defined as presence of plaque of any degree (1–49% or ≥50% diameter stenosis) or segments not assessable due to calcification in any of the 18 coronary segments. Analysis of severe atherosclerosis included participants with ≥50% diameter stenosis in any of the left main coronary artery (LMCA), the proximal left anterior descending artery (LAD) or three vessel disease including ≥50% diameter stenosis in any of the segments in each of the LAD, right coronary artery (RCA) and circumflex artery (CX). Participants with hsCRP above the lowest detection limit (≥0.7mg/L) were divided into tertiles and compared with hsCRP<0.7 mg/L as a reference. Results The highest tertile of measurable hsCRP (≥2.3 mg/L) was associated with coronary atherosclerosis in a multivariate analysis adjusted for classical cardiovascular risk factors (Table 1). HsCRP was also related to atherosclerosis with significant coronary artery diameter stenosis ≥50%, ≥4 segments involved, severe atherosclerosis and atherosclerosis with noncalcified plaques. Also, moderately elevated hsCRP (1.2–2.2 mg/L) was significant associated with noncalcified plaques. In a stratified analysis, coronary atherosclerosis was associated with the two highest tertiles of hsCRP (≥1.2 mg/L) in women, but not in men. Conclusion Elevated hsCRP was associated with the prevalence of coronary atherosclerosis in a population based cohort of middle-aged men and women. The relationships were more pronounced for atherosclerosis with noncalcified plaques and in women compared to men. This suggests that more attention should be given to hsCRP in risk assessment in middle-aged individuals without known disease, especially in women. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): The Swedish Heart Lung FoundationKnut and Alice Wallenberg Foundation

Statin dosage in patients with acute myocardial infarction (AMI) and concomitant kidney dysfunction is a clinical dilemma. We studied discontinuation during the first year after an AMI and long-term outcome in patients receiving high versus lowmoderate intensity statin treatment, in relation to kidney function. For the intention-to-treat analysis (ITT-A), we included all patients admitted to Swedish coronary care units for a first AMI between 2005 and 2016 that survived in-hospital, had known creatinine, and initiated statin therapy (N = 112,727). High intensity was initiated in 38.7% and low-moderate in 61.3%. In patients with estimated glomerular filtration rate (eGFR) , 60 mL/min/1.73 m 2 , 25% discontinued treatment the first year; however, the discontinuation rate was similar regardless of the statin intensity. After excluding patients who died, changed therapy, or were nonadherent during the first year, 84,705 remained for the on-treatment analysis (OT-A). Patients were followed for 12.6 (median 5.6) years. In patients with eGFR 30-59 mL/min, high-intensity statin was associated with lower risk for the composite death, reinfarction, or stroke both in ITT-A (hazard ratio [HR] 0.93; 95% confidence interval, 0.87-0.99) and OT-A (HR 0.90; 0.83-0.99); the interaction test for OT-A indicated no heterogeneity for the eGFR , 60 mL/min group (P = 0.46). Similar associations were seen for all-cause mortality. We confirm that high-intensity statin treatment is associated with improved long-term outcome after AMI in patients with reduced kidney function. Most patients with reduced kidney function initiated on high-intensity statins are persistent after 1 year and equally persistent as patients initiated on low-moderate intensity.

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