Drug-Induced Antibodies: Interaction of the Drug with a Polymorphic Platelet-Antigen

Preincubation of donor platelets with ticarcillin will prevent the reactivity of a platelet antibody against these platelets, whereas no influence was observed on antisera against HLA, 5A, 5b and ZWa. The implications for the mechanism of drug-induced antibodies with restricted specificity will be discussed.     

Effects of a long-distance run on cardiac markers in healthy athletes.

BACKGROUND: Running a marathon is a stressful event for athletes. Limited research exists on the role of cardiac markers during such a strenuous event. The aim of this study was to investigate detailed changes in cardiac markers before and after a long-distance run. METHODS: We studied 25 male and 2 female runners (age 34-64 years) who were running the Visé-Maastricht-Visé marathon. Blood samples were drawn just before and immediately after finishing the marathon. An additional blood sample was collected 24 h later. RESULTS: Running the marathon led to a significant increase in cortisol. This returned to baseline values 24 h after the marathon. There was a slight increase in brain natriuretic peptide (BNP); however, this was not statistically significant. On the contrary, the N-terminal fragment of BNP (NT-pro-BNP) was significantly increased immediately after the run and was normalized 24 h later in 26 out of 27 runners (96%). The magnitude of the transient elevations in BNP and NT-pro-BNP increased with the age of the athletes. Furthermore, in 9 out of 27 runners there was a significant increase in troponin T. However, in all these runners this increase was transient and troponin-T levels returned to baseline values 24 h after the marathon. CONCLUSIONS: Running a marathon significantly increases NT-pro-BNP levels in healthy adults. This increase could be partially attributed to cardiac stress. The transient increases in BNP, NT-pro-BNP and troponin T are more likely to reflect myocardial stunning than cardiomyocyte damage. It seems that the magnitude of the increase in BNP could serve as a marker of the biological age of the myocardium.     

Cotinine determination by immunoassays may be influenced by other nicotine metabolites

Polyclonal rabbit anticotinine antiserum, which can be used for biomonitoring nicotine uptake by the determination of cotinine in body fluids, was checked by a competitive ELISA for its cross-reactivity with nine nicotine metabolites. The highest percentage of relative crossreactivity (about 30%) was observed with trans-3-hydroxycotinine, a metabolite which is known to be excreted in 3-fold higher amounts than cotinine in the urine of human smokers. Therefore, it is possible that cotinine determinations performed by immunochemical methods — especially in urine — may yield overestimated cotinine concentrations.     

Preservation and redirection of HPV16E7-specific T cell receptors for immunotherapy of cervical cancer

Human papilloma virus (HPV) type 16 infections of the genital tract are associated with the development of cervical cancer (CxCa) in women. HPV16-derived oncoproteins E6 and E7 are expressed constitutively in these lesions and might therefore be attractive candidates for T-cell-mediated adoptive immunotherapy. However, the low precursor frequency of HPV16E7-specific T cells in patients and healthy donors hampers routine isolation of these cells for adoptive transfer. To overcome this problem, we have isolated T cell receptor (TCR) genes from four different HPV16E7-specific healthy donor and patient-derived human cytotoxic T lymphocyte (CTL) clones. We examined whether genetic engineering of peripheral blood-derived CD8+ T cells in order to express HPV16E711-20-specific TCRs is feasible for adoptive transfer purposes. Reporter cells (Jurkat/MA) carrying a transgenic TCR were shown to bind relevant but not irrelevant tetramers. Moreover, these TCR-transgenic Jurkat/MA cells showed reactivity towards relevant target cells, indicating proper functional activity of the TCRs isolated from already available T cell clones. We next introduced an HPV16E711-20-specific TCR into blood-derived, CD8+ recipient T cells. Transgenic CTL clones stained positive for tetramers presenting the relevant HPV16E711-20 epitope and biological activity of the TCR in transduced CTL was confirmed by lytic activity and by interferon (IFN)-gamma secretion upon antigen-specific stimulation. Importantly, we show recognition of the endogenously processed and HLA-A2 presented HPV16E711-20 CTL epitope by A9-TCR-transgenic T cells. Collectively, our data indicate that HPV16E7 TCR gene transfer is feasible as an alternative strategy to generate human HPV16E7-specific T cells for the treatment of patients suffering from cervical cancer and other HPV16-induced malignancies.     

Genotoxicity and physicochemical characteristics of traffic-related ambient particulate matter

Exposure to ambient particulate matter (PM) has been linked to several adverse health effects. Since vehicular traffic is a PM source of growing importance, we sampled total suspended particulate (TSP), PM(10), and PM(2.5) at six urban locations with pronounced differences in traffic intensity. The mutagenicity, DNA-adduct formation, and induction of oxidative DNA damage by the samples were studied as genotoxicological parameters, in relation to polycyclic aromatic hydrocarbon (PAH) levels, elemental composition, and radical-generating capacity (RGC) as chemical characteristics. We found pronounced differences in the genotoxicity and chemical characteristics of PM from the various locations, although we could not establish a correlation between traffic intensity and any of these characteristics for any of the PM size fractions. Therefore, the differences between locations may be due to local sources of PM, other than traffic. The concentration of total (carcinogenic) PAHs correlated positively with RGC, direct and S9-mediated mutagenicity, as well as the induction of DNA adducts and oxidative DNA damage. The interaction between total PAHs and transition metals correlated positively with DNA-adduct formation, particularly from the PM(2.5) fraction. RGC was not associated with one specific PM size fraction, but mutagenicity and DNA reactivity after metabolic activation were relatively high in PM(10) and PM(2.5), when compared with TSP. We conclude that the toxicological characteristics of urban PM samples show pronounced differences, even when PM concentrations at the sample sites are comparable. This implies that emission reduction strategies that take chemical and toxicological characteristics of PM into account may be useful for reducing the health risks associated with PM exposure.