Effects of an Educational Program on the Test Performance of Children with Psychoneurological Learning Disabilities

Student Personnel and Guidanc

Influenza A Virus Induces an Immediate Cytotoxic Activity in All Major Subsets of Peripheral Blood Mononuclear Cells

A replication defective influenza A vaccine virus (delNS1 virus) was developed. Its attenuation is due to potent stimulation of the innate immune system by the virus. Since the innate immune system can also target cancer cells, we reasoned that delNS1 virus induced immune-stimulation should also lead to the induction of innate cytotoxic effects towards cancer cells.Peripheral blood mononuclear cells (PBMCs), isolated CD56+, CD3+, CD14+ and CD19+ subsets and different combinations of the above subsets were stimulated by delNS1, wild type (wt) virus or heat inactivated virus and co-cultured with tumor cell lines in the presence or absence of antibodies against the interferon system. Stimulation of PBMCs by the delNS1 virus effectively induced cytotoxicity against different cancer cell lines. Surprisingly, virus induced cytotoxicity was exerted by all major subtypes of PBMCs including CD56+, CD3+, CD14+ and CD19+ cells. Virus induced cytotoxicity in CD3+, CD14+ and CD19+ cells was dependent on virus replication, whereas virus induced cytotoxicity in CD56+ cells was only dependent on the binding of the virus. Virus induced cytotoxicity of isolated cell cultures of CD14+, CD19+ or CD56+ cells could be partially blocked by antibodies against type I and type II (IFN) interferon. In contrast, virus induced cytotoxicity in the complete PBMC preparation could not be inhibited by blocking type I or type II IFN, indicating a redundant system of activation in whole blood.Our data suggest that apart from their well known specialized functions all main subsets of peripheral blood cells also initially exert a cytotoxic effect upon virus stimulation. This closely links the innate immune system to the adaptive immune response and renders delNS1 virus a potential therapeutic tool for viro-immunotherapy of cancer

Innate Immunity / The novel polyclonal Ab preparation trimodulin attenuates ex vivo endotoxin-induced immune reactions in early hyperinflammation

Sepsis is a syndrome associated with excessive inflammation. Since mortality from sepsis remains high, more laboratory research is needed to provide insight into more effective ways to use novel, potentially more beneficial agents in sepsis. We investigated the ex vivo immunomodulatory effect of a novel polyclonal Ab preparation, trimodulin, containing IgM (23%), IgA (21%) and IgG (56%). Using whole blood and purified PBMCs from healthy volunteers and patients with sepsis, various ex vivo investigations upon endotoxin challenge and pre- and post-trimodulin treatment were performed. Endotoxin-induced TNF- secretion was noticeably lower with than without trimodulin, implying attenuation of the hyper-responsive state. Trimodulin also lowered TLR2, TLR4, CD11b and CD64 detection on LPS/lipoteichoic acid-stimulated monocytes. These responses were observed in cells from healthy volunteers only shortly after ex vivo endotoxin stimulation and in whole blood from patients with early-stage sepsis. Furthermore, trimodulin markedly reduced lymphocyte proliferation and release of pro- and anti-inflammatory cytokines, but did not affect phagocytosis or oxidative-burst activities of endoxin-stimulated cells. Thus, trimodulin mitigated monocyte and lymphocyte hyperinflammatory responses early after endotoxin exposure. Determining whether early in vivo administration of trimodulin will elicit similar positive immunomodulatory effects and offer a clinical benefit warrants investigation.(VLID)510807

Comprehensive Evaluation of 11 Cytokines in Premature Infants with Surgical Necrotizing Enterocolitis

<div><p>Objective</p><p>A prospective study to investigate the pattern of pro- and anti-inflammatory cytokine responses in neonates with surgical necrotizing enterocolitis (NEC) and identify those cytokines being the most promising for future research.</p> <p>Methods</p><p>A panel of 11 different cytokines were measured in 9 infants with proven NEC and compared with 18 age-matched healthy neonates.</p> <p>Results</p><p>The serum concentrations of the interleukins (IL)-6, IL-8, and IL-10 were significantly (32–fold to 56-fold) higher in NEC infants compared with controls. In contrast, IL-5, IFN gamma, IL-4 and IL-2 showed slightly (1.4-fold to 5.9-fold) lower levels in the NEC samples. However, these cytokines showed a very low absolute concentration in infants with NEC and in controls. The sum of the serum concentrations of IL-6, IL-8 and IL-10 was able to clearly separate infants with NEC from control samples. IL-1 beta and TNF-alpha showed no statistically different levels. The serum levels of TNF-beta and IL-12p70 were below the detection limit in more than 50% of all samples per group.</p> <p>Conclusion</p><p>In spite of strong local inflammation only three out of eleven cytokines (IL-6, IL-8, and IL-10) showed strongly increased serum levels indicating an important role of them in the pathogenesis of NEC. At least two of these three cytokines were elevated in every single NEC patient. Thus, longitudinal monitoring of combined IL-8, IL-6, and IL-10 levels could reveal their potency in being clinical relevant markers in NEC.</p> </div

Neonatal characteristics of infants with NEC versus age matched controls.

a<p>median values; ^b at the time of diagnosis.</p

Clinical characteristics of infants with surgical NEC recruited for cytokine analysis.

<p>Patient nr.4 did not receive surgical treatment and was excluded.</p

Heat map and unsupervised hierarchical clustering of 9 NEC patients and 18 healthy age matched controls according to the serum levels of IL-6, IL-8, and IL-10.

<p>The colored heat map indicates the relative serum level of the respective interleukin: red represents the 0 percentile, black the 50% percentile and green the 100% percentile. The clustering was based on a median linkage analysis of the non-transformed serum levels using the Euclidean distance between cases (vertical cluster) or parameters (horizontal cluster). The numbers beneath the heat map indicates the summation of the serum concentration of all three cytokines (in pg/ml).</p

Serum concentrations of different interleukins in NEC patients (n = 9) and healthy age matched controls (n = 18).

<p>The median values of the respective group are indicated in the graph. Serum concentrations of Interleukin-12 (NEC and control group) and TNF-beta (NEC group) were below detection limit. The p-value was calculated using a Student's t-test.</p