An interfering component in cardiac troponin I immunoassays-Its nature and inhibiting effect on the binding of antibodies against different epitopes

OBJECTIVES: We recently reported on the occurrence of a common interfering factor (IF) that negatively affects determinations of cardiac troponin I (cTnI). The aim of the present investigation was to extend our initial finding by a detailed epitope-based determination of the location of IF and to reveal the approximate size and characteristics of IF. DESIGN AND METHODS: Two-site immunoassays using combinations of 16 monoclonal and 2 polyclonal cTnI antibodies and 1 monoclonal troponin C (TnC) antibody were used to measure the analytical recovery of cTnI or cTnI-TnC in serum samples. Gel filtration of serum samples containing IF was performed and the analytical recovery of cTnI in the fractions was determined. EDTA-plasma samples to which cTnI had been added and serum samples containing endogenous cTnI were also separated by gel filtration. RESULTS: The mean analytical recoveries of cTnI were 28.3% (range 7.5-55.1%) and of cTnI-TnC were 23.5% (range 8.7-51.8%) in samples containing IF when antibodies against midfragment epitopes of cTnI were used. The mean recovery of cTnI was 65.1% and 73.3% for antibodies with N- and C-terminal epitopes. Gel filtration of samples with low recovery of cTnI showed that the approximate molecular mass of IF was 50-200 kDa and that the cTnI elution profiles of samples containing IF were shifted towards higher molecular mass compared with samples with less IF. CONCLUSIONS: Antibodies against midfragment epitopes of cTnI are affected by IF to a considerable but variable extent, and the presence of IF can be demonstrated by gel filtration.     

NY-ESO-1 immunotherapy for multiple myeloma

Most patients with poor-prognosis myeloma (abnormal metaphase cytogenetics) achieve excellent responses with tandem transplants, but the remissions are not durable. Novel interventions such as immunotherapy may eradicate the residual chemotherapy-resistant disease. Immunotherapy targeting weak antigens such as myeloma idiotype or tumor lysate has failed to produce clinically meaningful responses. We previously reported that the NY-ESO-1 antigen is expressed in >60% of poor-prognosis myeloma at diagnosis. Since NY-ESO-1 is highly immunogenic and is not expressed in most normal tissues, it is an ideal target for anti-myeloma immunotherapy. NY-ESO-1 based therapies are already being tested in clinical trials for a multitude of tumors. This review discusses the potential of NY-ESO-1 immunotherapy to improve outcome for myeloma.     

Hepatitis C virus-derived lipopeptides differentially induce epitope-specific immune responses in vitro

We studied the induction of T cell responses against hepatitis C virus (HCV)-related cytotoxic T cell (CTL) epitopes in lymphocytes from human leukocyte antigen (HLA)-A2-positive, HCV-naive individuals. Peptide and lipopeptides corresponding to the epitope at amino acids (aa) 1073-1081 induced equivalent numbers of tetramer-positive CD8+ T cells and detectable interferon-gamma and granzyme B spot-forming cells (sfcs). Epitope aa 35-44 induction of CTLs was not achieved, despite detectable tetramer-positive CD8+ T cells. IFN-gamma sfcs could only be induced with lipopeptide aa 20-44 but not by conventional antigens, which indicates that lipopeptides may alter T cell functions, depending on the epitope.     

Assessment of hepatic ischemia-reperfusion injury by simultaneous measurement of tissue pO2, pCO2, and pH

INTRODUCTION: The objective of this study was to determine whether the simultaneous measurement of tissue pH, pCO(2), and pO(2) with a multiple-parameter fiberoptic sensor (Paratrend 7) can be used for continuous monitoring of hepatic microperfusion in a pig model of hepatic ischemia given endothelin(A) receptor antagonist (ET(A)-RA) or isotonic saline. METHODS: Fourteen anesthetized swine were subjected to 2 h of hepatic vascular exclusion. The animals were randomized into two groups: control group (n = 7, saline solution iv) and therapy group (n = 7, ET(A)-RA). For evaluation of ischemia-reperfusion injury, the data of the multiple-parameter sensor (pO(2para), pCO(2para), and pH(para)) were compared with partial oxygen pressure in tissue (p(ti)O(2)), laser Doppler flow, and systemic hemodynamic, metabolic data, and time course of transaminases. RESULTS: In the control group 30 and 60 min after reperfusion, the following values were measured: p(ti)O(2): 34.0 +/- 8.6 / 36.3 +/- 7.0 mm Hg (P < 0.05 vs. preop.: 49.8 +/- 12.1 mm Hg), laser Doppler area: 133.3 +/- 23.2 / 156.4 +/- 15.4 (P < 0.05 vs. preop.: 215.9 +/- 14.8). Animals in the therapy group revealed significantly improved values (p(ti)O(2): 54.0 +/- 8.6 / 58.1 +/- 7.8 mm Hg, laser Doppler: 210.2 +/- 38.5 / 225.2 +/- 21.3; P < 0.05). Using the Paratrend, also an improvement in the therapy group was seen 30 and 60 min after reperfusion. The values showed a strong correlation with p(ti)O(2) (r = 0.895; P < 0.05) and laser Doppler flow (r = 0.807; P < 0.05). In the treatment group, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and glutamate dehydrogenase (GLDH) were reduced 6 and 18 h after reperfusion, respectively, indicating hepatoprotection by the therapy (P < 0.05 vs. control). CONCLUSIONS: The Paratrend sensor offers the opportunity to study postischemic organ hemodynamics through the simultaneous measurement of interstitial pH, pCO(2), and pO(2) in a small tissue region. This method offers a prognostic tool for the study of the effects of experimental vasoactive therapy on liver microcirculation and perspectives for continuous monitoring of human liver microperfusion after liver surgery and trauma.     

Exposure to violent video games increases automatic aggressiveness

The effects of exposure to violent video games on automatic associations with the self were investigated in a sample of 121 students. Playing the violent video game Doom led participants to associate themselves with aggressive traits and actions on the Implicit Association Test. In addition, self-reported prior exposure to violent video games predicted automatic aggressive self-concept, above and beyond self-reported aggression. Results suggest that playing violent video games can lead to the automatic learning of aggressive self-views.     

Distinct methylation profiles of glioma subtypes

Gliomas are tumors of the central nervous system with a wide spectrum of different tumor types. They range from pilocytic astrocytoma, with a generally good prognosis, to the extremely aggressive malignant glioblastoma. In addition to these 2 types of contrasting neoplasms, several other subtypes can be distinguished, each characterized by specific phenotypic, as well as genotypic features. Recently, the epigenotype, as evident from differentially methylated DNA loci, has been proposed to be useful as a further criterion to distinguish between tumor types. In our study, we screened 139 tissue samples, including 33 pilocytic astrocytomas, 46 astrocytomas of different grades, 7 oligoastrocytomas, 10 oligodendrogliomas, 10 glioblastoma multiforme samples and 33 control tissues, for methylation at CpG islands of 15 different gene loci. We used the semiquantitative high throughput method MethyLight to analyze a gene panel comprising ARF, CDKN2B, RB1, APC, CDH1, ESR1, GSTP1, TGFBR2, THBS1, TIMP3, PTGS2, CTNNB1, CALCA, MYOD1 and HIC1. Seven of these loci showed tumor specific methylation changes. We found tissue as well as grade specific methylation profiles. Interestingly, pilocytic astrocytomas showed no evidence of CpG island hypermethylation, but were significantly hypomethylated, relative to control tissues, at MYOD1. Our results show that glioma subtypes have characteristic methylation profiles and, with the exception of pilocytic astrocytomas, show both locus specific hyper- as well as hypomethylation.     

Refractive lens exchange combined with pars plana vitrectomy to correct high myopia

PURPOSE: To describe the results of refractive lens exchange (RLE) combined with simultaneous pars plana vitrectomy (PPV) in the management of severe myopia. METHODS: This retrospective study comprised 14 eyes of eight patients who had RLE to treat myopia of -19.0+/-5.4 diopters (D). Phacoemulsification, posterior chamber intraocular lens (IOL) implantation, and standard three-port vitrectomy were performed. Mean postoperative follow-up time was 30 months (range 12-49). RESULTS: The postoperative best-corrected visual acuity (BCVA) was 0.68+/-0.23 compared to 0.37+/-0.24 preoperatively. There was no postoperative decrease in visual acuity in any eye. Mean postoperative spherical equivalent was -0.7 D (+/-1.6). At 30 months mean follow-up time, the spherical equivalents of nine eyes (64.3%) were within +/-1 D of emmetropia. There was no significant change in astigmatism due to operative procedures. During the 30 months follow-up period three eyes (21.4%) required neodymium : yttrium-aluminium-garnet (Nd : YAG) capsulotomy for posterior capsule opacification. No retinal detachments or cases of cystoid macular oedema (CME) were observed during the follow-up. CONCLUSION: RLE was effective in correcting severe myopia. The simultaneously performed PPV may reduce the risk of postoperative retinal detachment. This was a pilot study, to draw definitive conclusions a prospective study has to be initiated.     

Obesity in childhood and adolescence: a review in the interface between adipocyte physiology and clinical challenges

Body weight is regulated by a feedback loop in which peripheral signals report nutritional information to an integratory center in the brain. The cloning of the ob gene is consistent with this concept and suggests that body fat content in adult rodents is regulated by a negative feedback loop centered in the hypothalamus. In recent years a number of additional signaling molecules secreted by adipose tissue have been discovered. These hormones, named adipocytokines, include resistin, adiponectin, and visfatin. Among the adipocytokines, adiponectin is perhaps the most interesting compound for the clinician since low adiponectin serum levels have been found in obese subjects and in particular in insulin resistant subjects. The definition and diagnosis of obesity in children and adolescents are surprisingly difficult. The level of fatness at which morbidity increases is determined on an acturial basis. In children and adolescents the degree of body fat mass depends upon ethnic background , gender, developmental stage, and age. Treatment and prevention of obesity in childhood and adolescence are major challenges for today's health care providers and societies.