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Author(s): Susanne Westphal Ladfors [sup.1] [sup.2] , Jenny K. Lindahl [sup.3] [sup.4] , Sverker Hansson [sup.1] [sup.2] , Per Brandström [sup.1] [sup.2] , Rune Andersson [sup.3] [sup.4] , Marianne Jertborn [...], Background Epstein-Barr virus (EBV) infections can induce post-transplant lymphoproliferative disorder (PTLD). A chronic high load (CHL), as indicated by long-term high EBV DNA levels after transplantation, has been associated with an enhanced risk of PTLD. We aimed to evaluate incidence, time of occurrence, risk factors, and outcome of EBV CHL carrier state after pediatric renal transplantation. Methods A retrospective study of 58 children aged 1-17 years (median 10), who underwent renal transplantation between January 2004 and June 2017 at a single medical center. EBV IgG antibodies in serum were analyzed before and yearly after transplantation. EBV DNA in whole blood were analyzed weekly for the first 3 months post-transplant, monthly up to 1 year and then at least once yearly. CHL was defined as EBV DNA [greater than or equal to] 4.2 log.sub.10 Geq/ml in > 50% of the samples during [greater than or equal to] 6 months. Results At transplantation, 31 (53%) patients lacked EBV IgG and 25 (81%) of them developed primary EBV infection post-transplant. Of the 27 seropositive patients, 20 (74%) experienced reactivation of EBV. Altogether, 14 (24%) children developed CHL, starting at a median of 69 days post-transplant and lasting for a median time of 2.3 years (range 0.5-6.5), despite reduction of immunosuppression. Patients with CHL were younger and 11/14 were EBV seronegative at transplantation. No child developed PTLD during median clinical follow-up of 7.8 years (range 0.7-13). Conclusions CHL was frequent, long lasting, and occurred mainly in young transplant recipients. The absence of PTLD suggests that monitoring of EBV DNA to guide immunosuppression was effective.

The importance of inflammation in atherosclerosis is well established in cardiovascular disease. However, limited data exist on the relationship between vascular inflammation and the severity of peripheral arterial occlusive disease (PAD). We investigated the relationship between biochemical markers of vascular inflammation and the diagnostic measures of PAD: ankle–brachial pressure index (ABI), maximum treadmill walking distance and angiographic score. In 127 patients (mean age 66 years; 64% males) with angiographically verified PAD, fasting blood samples were drawn for determination of selected soluble cell adhesion molecules, cytokines and chemokines. Tumor necrosis factor-α (TNFα), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1) and CD40 ligand (CD40L) were all significantly correlated with the angiographic score (p < 0.05 for all). After adjustment for relevant co-variates, MCP-1 and CD40L remained statistically significant (p < 0.01 for both). IL-6 was, independent of other risk factors, inversely correlated with the maximum treadmill walking distance (p < 0.01). Our cross-sectional study in PAD patients showed that the vascular inflammatory markers MCP-1, CD40L and IL-6 were significantly associated with the extent of atherosclerosis, assessed by angiographic score and maximum treadmill walking distance. These findings indicate that vascular inflammation is implicated in PAD, which might be of importance in future diagnosis and treatment of the disease. [ABSTRACT FROM AUTHOR]

Benzamides induce sister chromatid exchanges (SCE) in L1210 cells. This induction is strongly potentiated when the cells are grown in nicotinamide-free medium. There is no dependence on the concentration of bromodeoxyuridine (BrdUrd) except at toxic doses, high enough to inhibit BrdUrd incorporation into the DNA. Nicotinamide starvation by itself does not increase the frequency of SCE markedly. These observations are consistent with the notion that BrdUrd and benzamides induce SCE by different mechanisms. The mode of action of benzamides in inducing SCE is still unclear. [ABSTRACT FROM PUBLISHER]

We demonstrate here that the carcinogen 15,16-dihydro-11-methylcyclopenta[a]phenanthren-17-one can cause sister chromatid exchange in human lymphocytes as well as it can cause mutation in bacterial cells and in V79 hamster cells. The non-methylated parent compound which has no tumorigenic action and yet significantly mutates both TA 100 and hamster V79 cells, has no effect on the frequency of sister chromatid exchange. These results support the idea that sister chromatid exchanges are a valuable additional indicator of tumorigenic potential. [ABSTRACT FROM PUBLISHER]

Human T lymphocyte proliferation induced by neuraminidase-galactose oxidase (NAGO)- treated autologous erythrocytes (HENAGO) plus polyethylene glycol (PEG) has previously been shown to be independent of accessory cells. Here, we show that the response to HENAGO+ PEG was accompanied by interleukin 2 (IL-2) release and was inhibited by anti-IL-2 and anti-IL-2 receptor antibodies. HENAGO alone initiated DNA synthesis together with phorbol ester (12-O-tetradecanoyl-phorbol-13-acetate; TPA). To elucidate the nature of the stimulatory signals NAGO-treated sheep erythrocytes (SENAGO) were used in additional experiments. In parallel to the superior rosetting capacity of SE compared to HE, SENAGO were by themselves stimulatory, and the response was further enhanced by PEG or TPA. Antibody L180/1, specific for the T11 (CD2) target structure (T11TS) on SE, homologous to the human CD2 ligand LFA-3, abolished the response to SENAGO alone or when combined with PEG or TPA. The results suggest that ENAGO induce T-cell response through CD2-LFA-3-T11TS interaction, and via other surface antigens bound by the oxidatively induced aldehyde groups on ENAGO. [ABSTRACT FROM AUTHOR]

Human peripheral lymphocytes were cultivated in soft agar or agarose, containing ³H-thymidine or bromodeoxyuridine (BrdU), which is an analogue of thymidine readily incorporated into deoxyribonucleic acid by lymphocytes. Colonies were isolated and analysed by autoradiography or stained with the fluorescence-plus-Giemsa technique, which identifies cells that have passed one, two, three, or more replication cycles with incorporation of BrdU. Colonies contained cells in their first and second division cycle together with later generations. The labelling index was very high. Consequently, it was concluded that, at least without special precautions being taken, lymphocyte colonies in semi-liquid medium are likely to grow through recruitment of mobile cells as well as through divisions within the colonies. Thus, T-cell growth in gels seems to be a matter of recognition between activated blast cells rather than monoclonal growth. [ABSTRACT FROM AUTHOR]