Abstract: Background and purpose:  Inflammatory cytokines are involved in the systemic inflammation, which precedes an ischaemic stroke (IS), and also participate into brain ischaemia-reperfusion injury. We sought to investigate whether functional polymorphisms of two anti-inflammatory molecules, interleukin (IL)4-589C>T and IL10-1082G>A, might be associated with the occurrence, clinical course and functional outcome of an acute IS. Methods:  We genotyped 290 subjects (145 consecutive IS cases and 145 age- and sex-matched controls) using a real-time PCR technology, prototypically designed for these mutations. Patients were evaluated with the Scandinavian Stroke Scale, and definitions of severity grouping and stroke progression were applied based on international agreements. Follow-up on months 1, 3, and 6 included registration of disease relapses, deaths and functional outcome measured by the Barthel Index. Results:  IL4-589 and IL10-1082 genotypes did not significantly differ between cases and controls. The presence of IL4-589 T allele was associated with total IS recurrences [OR (95% CI) = 3.34 (1.18-9.45)], adjusted for age, sex and conventional risk factors. IL10-1082 GG genotype was found to significantly predict early stroke progression [OR (95% CI) = 3.72 (1.28-10.76)] and functional outcome by months 1 and 3 [OR (95% CI) = 5.03 (1.15-21.94) and 5.84 (1.07-31.85), respectively], after further corrections for stroke severity and TOAST categories. Conclusions:  The functional IL4-589C>T and IL10-1082G>A polymorphisms seem not to be associated with occurrence of an IS, but may predict IS relapses, progressing strokes and functional outcome, independently of conventional risk factors. Our results merit further confirmation in future studies.
Abstract: survivin is involved in the regulation of cell division and survival, two key processes in cancer. The majority of studies on survivin in colorectal cancer (CRC) have focused on protein expression and less is known about the expression of survivin splicing variants or survivin gene polymorphisms in CRC. In the present study, the mRNA levels of the five known isoforms of survivin as well as survivin protein were assessed in matched normal and neoplastic colorectal tissue. Moreover, the 9386C/T and -31G/C polymorphisms were investigated.
Abstract: Past ischemic stroke (IS) patients display suppressed adiponectin (ADPN) levels a few months after disease onset. It is still unclear whether hypoadiponectinemia is already present by the early stages of stroke or occurs as a delayed effect of the acute ischemic reaction. In the present study we investigated ADPN levels acutely after an IS.
Abstract: The prion protein, PrP(C), is known mostly for its involvement in neurodegenerative spongiform encephalopathies. However, a role for this molecule in cancer is becoming increasingly recognized partly because it promotes cell proliferation and inhibits apoptosis. Moreover, the codon 129 polymorphism (M129V) of the PRNP gene (the PrP(C)-encoding gene) has been associated with neurodegenerative disease development and severity, while no information is available regarding its role in colorectal cancer (CRC) incidence and disease progression. We have previously reported that expression levels of PRNP may have a prognostic value in CRC, suggesting a role for the prion protein in CRC. The aim of this study was to investigate retrospectively the possible role of M129V and PrP(C) expression in patients with CRC. The M129V single nucleotide polymorphism was genotyped by real time polymerase chain reactions in 110 patients with CRC and 124 healthy donors. Moreover, protein expression was assessed by immunohistochemistry in 68 patients with CRC. Allele frequencies were similar in patients and healthy controls indicating that the M129V polymorphism is not a risk factor for CRC. Furthermore, it did not correlate with any clinicopathological parameters. By contrast, PrP(C) expression was highly elevated in neoplastic compared to normal tissue and differed depending on the primary site. Interestingly, protein levels were correlated with disease recurrence (P = 0.007). Conclusively, PrP(C) overexpression may constitute a prognostic marker for disease recurrence and potentially a new target for anticancer therapy. However, further studies are needed to evaluate prospectively the role of PrP(C) expression in patients with CRC.
Abstract: BACKGROUND: Circulating adiponectin (ADPN) has been inversely associated with the risk of coronary artery disease and ischemic stroke (IS), due to its anti-inflammatory and anti-atherosclerotic properties. Recent experimental studies have suggested that ADPN may as well exert cerebroprotective properties in brain ischemia, therefore modifying disease outcome. We investigated whether acute post-stroke ADPN in humans might be associated with disease severity, progression and outcome. METHODS: Serum ADPN was measured in 82 consecutive acute IS patients. Severity at presentation and stroke progression within the first week were evaluated according to internationally agreed definitions. Disability and functional outcomes were assessed on months 1, 3 and 6 using the modified Rankin scale (mRS) and Barthel index (BI). Additional data included information on infarct size, mortality, recurrent IS and mental state. RESULTS: Higher ADPN was indicative of greater disability (mRS) on month 1 (OR=1.141, 95% CI=1.012-1.286, p=0.031), but this result was not replicated using the BI. ADPN was not found to be associated with either stroke severity, clinical progression, infarct size, recurrent IS, mortality, mental state, disability or functional outcome during the 6 month follow-up. CONCLUSIONS: Despite previous experimental evidence, serum ADPN measured shortly after an acute IS in humans does not seem to reliably predict disease severity, progression or outcome. The concept that circulating ADPN may beneficially modify long-term outcome of an acute IS may not be the case for human stroke.
Abstract: Local humoral and cellular immune responses modulate the inflammatory processes involved in the development of atherosclerotic lesions, as well as in the evolution of brain infarcts in stroke patients. The role of systemic adaptive immunity on the progression of such disease manifestations is less clear. In the current study, we evaluated the percentages of T helper 1 (Th1) [interleukin (IL)-2, interferon (IFN)-gamma] and Th2 (IL-4, IL-10) cytokine-producing peripheral blood CD4+ and CD8+ T cells in 23 patients with a history of ischaemic stroke (IS) at the chronic stable phase of the disease (median post-stroke time 34.5 months). Seven stroke-free individuals matched for age and vascular risk factors (matched controls, MC) were collected for comparison. To measure cytokine values at baseline and after stimulation, we used a flow cytometry method of intracellular cytokine staining. Intrinsic Th1 and Th2 cytokine production in unstimulated T cells was negligible in all study participants. Following mitogenic stimulation with phorbol 12-myristate13-acetate/ionomycin, both the IS and the MC groups exhibited a similarly strong Th1 response; IL-2 production predominated in the CD4+ T cells and IFN-gamma in the CD8+ T cells. However, when measuring the Th2 cytokine-production capacity post-stimulation, a significant increase in the percentage of IL-4-producing T cells was observed in the IS groups, compared with the MC group, resulting in a significantly lower ratio of IFN-gamma-/IL-4-producing T cells. No such Th2 enhancement could be confirmed for the case of IL-10. We propose that in IS patients there is a systemic shift of the immune system towards Th2 responses at the late post-acute phase of stroke.
