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Background Phlegmonous and gangrenous appendicitis represent independent pathophysiological entities with different clinical courses ranging from spontaneous resolution to septic disease. However, reliable predictive methods for these clinical phenotypes have not yet been established. In an attempt to provide pathophysiological insights into the matter, a genomewide gene expression analysis was undertaken in patients with acute appendicitis. Methods Peripheral blood mononuclear cells were isolated and, after histological confirmation of PA or GA, analysed for genomewide gene expression profiling using RNA microarray technology and subsequent pathway analysis. Results Samples from 29 patients aged 7–17 years were included. Genomewide gene expression analysis was performed on 13 samples of phlegmonous and 16 of gangrenous appendicitis. From a total of 56 666 genes, 3594 were significantly differently expressed. Distinct interaction between T and B cells in the phlegmonous appendicitis group was suggested by overexpression of T cell receptor α and β subunits, CD2, CD3, MHC II, CD40L, and the B cell markers CD72 and CD79, indicating an antiviral mechanism. In the gangrenous appendicitis group, expression of genes delineating antibacterial mechanisms was found. Conclusion These results provide evidence for different and independent gene expression in phlegmonous and gangrenous appendicitis in general, but also suggest distinct immunological patterns for the respective entities. In particular, the findings are compatible with previous evidence of spontaneous resolution in phlegmonous and progressive disease in gangrenous appendicitis.

Die septische Granulomatose („chronic granulomatous disease“, CGD) ist ein angeborener Immundefekt mit rezidivierenden Infektionen sowie erhohtem Risiko fur Autoimmunerkrankungen und Autoinflammation. Die Prognose der Erkrankung wurde masgeblich durch eine fruhe Diagnose und die fruhe Stammzelltransplantation verbessert. Beschrieben wird der Fall eines 11 Monate alten Jungen, der bei rezidiverem Fieber mit unklarem Fokus und Hepatosplenomegalie aufgenommen wurde. Er ist das erste Kind eines deutschen unverwandten Paares. Fieber trat erstmalig im 4. Lebensmonat auf und rezidivierte im 5, 8. und 11. Lebensmonat. Der wegweisende Befund einer massiven Lymphknotenschwellung fuhrte zur Verdachtsdiagnose einer infektiosen Lymphadenitis auf Grundlage einer Phagozytenfunktionsstorung. Die Diagnose einer CGD wurde funktionell und molekular gesichert. Wir behandelten das Kind initial mit i.v.-verabreichtem Antibiotikum uber 6 Wochen und empfahlen die Durchfuhrung einer „Reduced-intensity“-Stammzelltransplantation, die im Alter von 14 Monaten erfolgreich und komplikationslos erfolgte. Die elektive Stammzelltransplantation ist die einzige kurative Therapie der CGD und sollte daher allen Patienten mit einem 10/10 HLA-passenden Spender dringend empfohlen werden.

Fanconi anemia (FA) is a genomic instability syndrome associated with bone marrow failure, myelodysplastic syndrome (MDS), and/or acute myeloid leukemia (AML) requiring hematopoietic stem cell transplantation (HSCT) to restore normal hematopoiesis. Although low-intensity fludarabine-based preparative regimens without radiation confer excellent outcomes in FA HSCTs with HLA-matched sibling donors, outcomes for FA patients with alternative donors are less encouraging, albeit improving. We present our experience with 17 FA patients who completed mismatched related or unrelated donor HSCT using a non-radiation fludarabine-based preparative regimen at Charité University Medicine Berlin. All patients engrafted; however, one patient had unstable chimerism in the setting of multi-viral infections that necessitated a stem cell boost to revert to full donor chimerism. Forty-seven percent of patients developed grade I acute graft-verus-host disease (aGVHD). No grade II-IV aGVHD or chronic graft-versus-host disease of any severity occurred. At a median follow-up of 30 months, 88 % of patients are alive with normal hematopoiesis. Two patients died of infections 4 months post-transplantation. These results demonstrate that short-term outcomes for FA patients with mismatched and unrelated donor HSCTs can be excellent using chemotherapy only conditioning. Viral reactivation, however, was a major treatment-related complication.

X-linked inhibitor of apoptosis (XIAP) deficiency caused by mutations in BIRC4 was initially described in patients with X-linked lymphoproliferative syndrome (XLP) who had no mutations in SH2D1A. In the initial reports, EBV-associated hemophagocytic lymphohistiocytosis (HLH) was the predominant clinical phenotype. Among 25 symptomatic patients diagnosed with XIAP deficiency, we identified 17 patients who initially presented with manifestations other than HLH. These included Crohn-like bowel disease (n=6), severe infectious mononucleosis (n=4), isolated splenomegaly (n=3), uveitis (n=1), periodic fever (n=1), fistulating skin abscesses (n=1) and severe Giardia enteritis (n=1). Subsequent manifestations included celiac-like disease, antibody deficiency, splenomegaly and partial HLH. Screening by flow cytometry identified 14 of 17 patients in our cohort. However, neither genotype nor protein expression nor results from cell death studies were clearly associated with the clinical phenotype. Only mutation analysis can reliably identify affected patients. XIAP deficiency must be considered in a wide range of clinical presentations.

ZusammenfassungPrimäre Immundefekte werden in der tägli-chen Praxis oftmals noch zu spät diagnostiziert. Die hier vorliegende AWMF-Leitlinie (S2k) zur Diagnostik von primären Immundefekten wurde mit dem Ziel erstellt, die Diagnoserate von Patienten mit primären Immundefekten zu erhöhen. Durch die Möglichkeit einer rechtzeitigen Therapieeinleitung soll die Morbidität und Mortalität der betroffenen Patienten verringert werden. Die Leitlinie beinhaltet modifizierte Warnzeichen für primäre Immundefekte, sowie Empfehlungen zur Basisdiagnostik und eine Definition von immunologischen Notfallsituationen.

Primare Immundefekte sind potenziell lebensbedrohliche Erkrankungen. Auch wenn in den letzten Jahren zunehmend mehr immunologische Defekte klinisch und molekulargenetisch charakterisiert wurden, so werden primare Immundefekt in der taglichen Praxis oftmals noch zu spat erkannt. Vor dem Hintergrund, dass eine fruhe Diagnosestellung die Morbiditat und Mortalitat der betroffenen Patienten senken kann, wurde daher im Auftrag der Arbeitsgemeinschaft Padiatrische Immunologie (API) und der Deutschen Gesellschaft fur Immunologie (DGfI) eine interdisziplinare S2-Leitlinie zur Diagnostik von Primaren Immundefekten erstellt. Grundlage der Leitlinie sind im Wesentlichen Expertenmeinungen auf der Basis bereits verfugbarer Leitlinien und Empfehlungen aus Deutschland und anderen Landern, erganzt durch Daten aus Studien, die die getroffenen Kernaussagen unterstutzen (Evidenzgrad III). Unter Beteiligung von 20 Vertretern aus 14 Fachgesellschaften, Verbanden und Vereinigungen entstand eine konsensbasierte Leitlinie mit reprasentativer Entwicklergruppe und strukturierter Konsensusfindung (S2k). Der nominale Gruppenprozess zur Konsensusfindung fand unter Moderation einer Vertreterin der Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (e.V.) (AWMF) im April 2011 statt. Die aufgestellten Kernaussagen wurden diskutiert und im strukturierten Konsensverfahren abgestimmt. Insbesondere wurden modifizierte Warnzeichen fur primare Immundefekte formuliert und immunologische Notfallsituationen definiert.

Die Basisdiagnostik bei Verdacht auf Immundefekt soll die meisten lebensbedrohlichen und haufige immunologische Erkrankungen detektieren. Sie umfasst ein mikroskopisch differenziertes Blutbild und die Bestimmung von IgG, IgA, IgM und IgE (Ig: Immunglobulin). Ein SCID („severe combined immunodeficiency“) kann oft bereits anhand der meist (aber nicht immer!) vorhandenen Lymphopenie und dem Mangel an IgM diagnostiziert werden. Fur CVID („common variable immunodeficiency“) sprechen ein persistierender IgG-Mangel nach Abschluss des 2. Lebensjahrs, ausgeschlossene sekundare Ursachen des Antikorpermangels, 2 von 3 reduzierte Immunglobulinklassen und reduzierte Impfantikorpertiter. Durch diese immunologische Basisdiagnostik lassen sich vermutlich nur 40–50% der bisher bekannten Immundefekte erkennen. Die am klinischen Bild (Erreger, Art, Schwere und Verlauf der Infektion, syndromale Manifestationen, Zeichen einer gestorten Immunregulation) und den Ergebnissen der Basisdiagnostik ausgerichtete erweiterte immunologische Diagnostik ermoglicht eine Eingrenzung des Immundefekts. Die exakte Beschreibung des klinisch-immunologischen Phanotyps ist Voraussetzung fur eine gezielte molekulargenetische Diagnostik.

Background Usually IL-7 receptor deficiency presents as (T-B+NK+) (Severe) Combined Immunodeficiency (SCID) within the first six months of life. All published IL-7R-deficient patients so far have been diagnosed and received stem cell transplantation within the first year of life. Patient and methods We present a female patient born to non-consanguineous German parents with delayed manifestation. She presented with superinfected dermatitis at 6 months of life and developed a first pneumonia at age 9 months. On admission to our department at 22 months the patient presented with severe T cell lymphopenia. PNEUMOCYSTIS JIROVECI pneumonia was diagnosed from broncho-alveolar lavage fluid. Results Sequencing of IL7RA in the patient revealed compound heterozygous mutations. FACS analysis showed no expression of IL-7 receptor alpha-chain on the patient's lympho- and monocytes. The patient successfully received haematopoietic stem cell transplantation from a 9/10 matched unrelated donor at age 24 months. Conclusion [corrected] Despite almost absent T cell functions clinical symptoms occurred late compared to previously published patients. Thus even in patients with moderate clinical symptoms and delayed onset a (T-B+NK+) (Severe) Combined Immunodeficiency ((S)CID)) due to missing IL-7 receptor signalling must be considered.

Klassische angeborene Immundefekte pradisponieren zu wiederholten, oft polytopen schweren Infektionen durch multiple opportunistische Erreger. In den letzten 10 Jahren sind auch genetisch bedingte Immundefekte mit selektiver Anfalligkeit fur Infektionen durch einzelne Erregergruppen oder einzelne Erreger identifiziert worden. Hierzu gehoren Immundefekte mit Pradisposition fur Infektionen durch Mykobakterien und Salmonellen, fur invasive bakterielle Infektionen, fur Herpes-simplex-Enzephalitis, fur durch Epstein-Barr-Virus induzierte lymphoproliferative Krankheitsbilder und fur schwere Infektionen durch Papillomaviren. Die folgende Ubersicht stellt Genetik, Pathophysiologie, klinisches Bild, Differenzialdiagnosen, diagnostisches Vorgehen, Prognose und Therapieoptionen dieser „neuen“ Immundefekte dar.

SUMMARY Twelve exteroceptive skin reflexes were studied in three behavioural states:–regular sleep, irregular sleep and wakefulness–in twenty normal full-term infants. In the finger and toe reflexes highly significant differences were observed in the three states. A moderate state dependency was found in the foot, tibial, fibular, thigh, and lateral abdominal reflexes. No changes of the reflex intensity were observed in the axillary, pubic, and inguinal reflexes. The speculation was discussed that reflexes without any state dependency have a protective character. The trigemino-facial reflex was always absent in some babies and in others always present, without any differences in states. The rooting reflex was absent in both sleep states. RESUME Dependence des reflexes cutanis exteroceptifs chez les enfants nouveaux-nes en fonction du niveau de conscience Douze reflexes cutanes exteroceptifs ont eteetudies dans trois niveaux de comportement different: sommeil regulier, sommeil irregulier et eveil, chez 20 enfants nouveaux-nes, nes a terme, normaux. Dans les reflexes du doigt et de l'orteil, des differences hautement significatives ont ete observees entre les trois etats. Une relation plus moderee avec l'etat de comportement a ete trouvee dans les reflexes du pied, du tibia, du perone, de la cuisse ainsi que le reflexe abdominal lateral. On n'a pas observe de variations d'intensite du reflexe pour les reflexes axillaires, pubiens et inguinaux. On discute Phypothese que les reflexes qui ne sont pas modifies par I'etat de comportement ont un caractere de protection. Le ieflexe trigemino-facial etait toujours absent chez quelques enfants et toujours present chez d'autres, sans difference en fonction de I'etat de comportement. Le ‘rooting reflex’ fut trouve absent dans les deux etats de sommeil. ZUSAMMENFASSUNG Die Zustandsabhangigkeit der exteroceptiven Hautreflexe bei neugeborenen Kindern ZwOlf exteroceptive Hautreflexe wurden in drei Veihaltenszustanden untersucht: ruhiger Schlaf, unruhiger Schlaf und Wachzustand, bei zwanzig normalen reifen Neugeborenen. Bei den Finger- und Zehen-Reflexen wurden hoch signifikante Unterschiede zwischen den drei Zustanden beobachtet. Eine mittlere Zustandsabhangigkeit wurde bei den Fus-, Tibia-, Fibula, Oberschenkel- und lateralen Bauchreflexen gefunden. Keine Intensitats-unterschiede wurden bei den axillaren-, pubischen- und inguinalen Reflexen festgestellt. Es wurde die Uberlegung diskutiert, das die Reflexe ohne jegliche Zustandsabhangigkeit eine Schutzfunktion haben. Der Trigemino-faciale Reflex war bei einigen Babies nie, bei anderen immer vorhanden ohne Unterschiede in den einzelnen Phasen. Der ‘Rooting-Reflex’ (Brustsuchen) fehlte in beiden Schlafstadien. RESUMEN Dependencia del estado (despierto o dormido) de reflejos cutaneos exteroceptivos en reciin nacidos Se estudiaron doce reflejos cutaneos exteroceptivos en tres estados de comportamiento: suefto regular, sueno inegular, y estado de vigilia, en veinte recien necidos sanos nacidos a termino. En el reflejo digital, tanto de la mano como del pie, se hallaron diferencias muy significativas en los tres estados. Se hallo una moderada relacion del estado con los reflejos plantar, tibial, fibular, femural, y abdomino-lateral. No se advirtio ningiin cambio en la intensidad del reflejo en los reflejos axilar, pubico, e inguinal. Se discute la idea de que reflejos que no dependen del estado tengan un caracter protector. En algunos lactantes el reflejo trigemino-facial era siempre presente, y en otros siempre ausente, en todos los tres estados. El reflejo de ‘rooting’ (busqueda del pecho) no se veia en los dos estados de sueno.

A 16 year old lebanese girl with consanguinous parents presented with a severe “abdominal” sepsis supposedly resulting from an infected vaginal tampon (ESBL E.coli). She had been healthy before. She developed severe hepatic functional disorder, infarction of the spleen, cardiovascular and renal insufficiency, as well as anemia and thrombocytopenia. Macrophage activation syndrome was diagnosed subsequently and systemic glucocorticoid treatment initiated. The girl recovered clinically. Of note, she developed severe cushingoid syndrome. Due to limited compliance she discontinued all anti-inflammatory medication (nsaids, gc and ciclosporin) 4 weeks later. The following 18 months inflammatory parameters were persistantly elevated (ESR>100mm/h). Familial mediteranean fever was excluded. Genetic analysis revealed a homozygous perforin I gene mutation 91 (GCG) -> Valin (GTG)/.pAla91Val-/A91V in exon 2. Familial hemophagocytic lymphohistiocytosis type II was discussed as a potential diagnosis. Perforin expression was diminshed to about 50% in NK-cells, however functional NK-cell cytotoxicity was in the lower normal range, considered not impaired. On the basis of these findings, we want to discuss the role of the homozygous A91V perforin mutation for the initiation or perpetuation of a life-threatening macrophage activation syndrome, in addition to the further management of the patient.

The classic primary immunodeficiencies confer predisposition to multiple infectious diseases. However since ten years severe pediatric infections which were idiopathic have now molecular explanation. Indeed, defects in several genes confer a predisposition to infection with specific pathogenes in otherwise healthy individuals. These children present a new kind of hereditary immunodeficiency with severe and/or recurrent infections caused by only one microorganisms family, in opposition of others patients with "classic" primary immunodeficiency.

Hintergrund. Patienten mit septischer Granulomatose (CGD) leiden nicht nur an oft lebensbedrohlichen Infektionen, sondern auch an granulomatosen Entzundungen, fur welche neben einer Erregerpersistenz uberwiegend erregerunabhangige Pathomechanismen verantwortlich gemacht werden.Auch granulomatose Entzundungen ohne primaren Erregernachweis konnen bei Patienten mit septischer Granulomatose mit lebensbedrohlichen Komplikationen verbunden sein. Methoden und Patienten. Bei 6 Patienten konnten entzundlich veranderte Organe radiologisch, sonographisch und histologisch nachgewiesen werden.Nach bestmoglichem Ausschluss einer infektiosen Ursache wurden 5 Patienten mit Steroiden und 1 Patient mit Mesalazin behandelt und uber einen Zeitraum von 1-5 Jahren nachbeobachtet. Ergebnisse. Die entzundlichen Organveranderungen bildeten sich bei allen 6 Patienten zuruck bzw. schritten nicht fort.Dies war teilweise mit einer entscheidenden Besserung bedrohlich eingeschrankter Organfunktion verbunden.Durchbruchinfektionen wurden nicht beobachtet. Schlussfolgerung. Nach sorgfaltigem Ausschluss einer infektiosen Ursache und unter angemessener antimikrobieller Prophylaxe gegen Pilze und Bakterien sollten granulomatose Entzundungen bei Patienten mit CGD immunsuppressiv behandelt werden. Bei schwerem klinischem Verlauf einer solchen Entzundung ist eine Therapie mit Steroiden obligat.

Background. Cell-mediated immune responses can be down-regulated by induction of apoptosis of immunoreactive lymphocytes. In the present study, we have tested the feasibility of a strategy for immunosuppression by the selective induction of apoptosis in activated, interleukin (IL)-2 receptor-positive lymphocytes, using a triple IL-2-IgG-FasL fusion protein. The IL-2-IgG-FasL fusion protein combines IL-2 for the selection of activated T cells, with the extracellular domain of the FasL molecule for inducing T-cell apoptosis. These components were separated by the Fc part of IgG1 serving as a spacer as well as for half-life prolongation. Methods. The gene for the chimeric protein was created by fusing DNA sequences encoding for the three functional components: human IL-2, the Fc part of human IgG1, and the extracellular domain of murine FasL. When the fusion gene was expressed in murine J558L cells, we obtained soluble dimeric immunoglobulin-like proteins in the supernatant. After analyzing the function of the IL-2 and FasL portions individually in vitro, a delayed-type hypersensitivity (DTH) reaction to sheep red blood cells as model for cell-mediated immune responses was investigated to evaluate the IL-2-IgG-FasL-mediated immunosuppression in vivo. Results. In vitro, the IL-2-IgG-FasL fusion protein supported IL-2-dependent proliferation of Fas-resistant CTLL-2 cells, whereas concanavalin A-T blasts were induced to undergo apoptosis by the FasL portion. In vivo, this fusion protein potently inhibited a murine DTH. This was associated with an increased rate of apoptosis in activated lymphocytes in the spleen, even at very low doses of the fusion protein. Furthermore, a second antigen challenge 10 days after IL-2-IgG-FasL treatment still failed to elicit a DTH response. Conclusion. The abrogation of a standard T cell-dependent immune response in vivo demonstrates that IL-2-IgG-FasL can be successfully exploited to trigger the death of deleterious T cells, presenting a potentially useful strategy in the management of autoimmune diseases and allotransplant rejections.

Primary immunodeficiencies are potentially life-threatening diseases. Over the last years, the clinical phenotype and the molecular basis of an increasing number of immunological defects have been characterized. However, in daily practice primary immunodeficiencies are still often diagnosed too late. Considering that an early diagnosis may reduce morbidity and mortality of affected patients, an interdisciplinary guideline for the diagnosis of primary immunodeficiencies was developed on behalf of the Arbeitsgemeinschaft Pädiatrische Immunologie (API) and the Deutsche Gesellschaft für Immunologie (DGfI).The guideline is based on expert opinion and on knowledge from other guidelines and recommendations from Germany and other countries, supplemented by data from studies that support the postulated key messages (level of evidence III). With the contribution of 20 representatives, belonging to 14 different medical societies and associations, a consensus-based guideline with a representative group of developers and a structured consensus process was created (S2k). Under the moderation of a representative of the Association of the Scientific Medical Societies in Germany (AWMF) the nominal group process took place in April 2011.The postulated key messages were discussed and voted on following a structured consensus procedure. In particular, modified warning signs for primary immunodeficiencies were formulated and immunological emergency situations were defined.

Adenosin deaminase (ADA) deficiency is the cause for Severe Combined Immunodeficiency (SCID) in about 15% of patients with SCID, often presenting as T (-)B (-)NK (-)SCID. Treatment options for ADA-SCID are enzyme replacement, bone marrow transplantation or gene therapy. We here describe the first patient with ADA-SCID and fatal hepatic failure despite bone marrow transplantation from a 10/10 HLA identical related donor. As patients with ADA-SCID may be at yet underestimated increased risk for rapid hepatic failure we speculate whether hepatitis in ADA-SCID should lead to the immediate treatment with enzyme replacement by pegylated ADA.

Background Familial Mediterranean Fever (FMF) is an autoinflammatory disorder associated with MEFV pyrin-encoding gene mutations. S100A12 is a pro-inflammatory “damage associated molecular pattern” molecule and is strongly elevated in active FMF Objectives To investigate the association between genotype and S100A12 secretion in clinically active, inactive and subclinical disease in vitro and ex vivo . Methods Serum S100A12 concentration was retrospectively analysed for 125 patients in the German Auto-Inflammatory Diseases Network (AID-Net) Registry according to disease activity and genotype. In vitro , secretion of S100A12, IL-18, IL-1beta and caspase-1 was measured after stimulation of neutrophils from six M694V -positive patients and four healthy controls (HC). Results S100A12 hypersecretion correlated significantly with clinical disease activity and also with genotype in a “gene-dosing” way, being highest in homozygotes > compound heterozygotes > heterozygotes. M694V -positive heterozygous, compound heterozygous or homozygous patients h had higher S100A12 concentration during inactive and subclinical disease than M694V- negative heterozygous, compound heterozygous or homozygous patients respectively. In vitro , unstimulated neutrophils from M694V -positive patient spontaneously secreted higher S100A12, IL-8 and caspase-1 compared to healthy controls. Colchicine significantly inhibited secretion of S100A12 from stimulated and unstimulated patient neutrophils. Conclusions FMF phenotype is known to be more severe in patients with M694V mutations. We describe for the first time a biomarker that correlates with clinical disease activity and FMF genotype both ex vivo and in vitro , which has implications for clinical management. References Wittkowski H. et al. Pediatr Rheumatol 2008. Kallinich T. et al. ARD 2010. Jeske M et al. Klin Padiatrie 2013. Disclosure of Interest None declared

The classic primary immunodeficiencies confer predisposition to multiple infectious diseases. However since ten years severe pediatric infections which were idiopathic have now molecular explanation. Indeed, defects in several genes confer a predisposition to infection with specific pathogenes in otherwise healthy individuals. These children present a new kind of hereditary immunodeficiency with severe and/or recurrent infections caused by only one microorganisms family, in opposition of others patients with "classic" primary immunodeficiency.

Cell-mediated immune responses can be down-regulated by induction of apoptosis of immunoreactive lymphocytes. In the present study, we have tested the feasibility of a strategy for immunosuppression by the selective induction of apoptosis in activated, interleukin (IL)-2 receptor-positive lymphocytes, using a triple IL-2-IgG-FasL fusion protein. The IL-2-IgG-FasL fusion protein combines IL-2 for the selection of activated T cells, with the extracellular domain of the FasL molecule for inducing T-cell apoptosis. These components were separated by the Fc part of IgG1 serving as a spacer as well as for half-life prolongation.The gene for the chimeric protein was created by fusing DNA sequences encoding for the three functional components: human IL-2, the Fc part of human IgG1, and the extracellular domain of murine FasL. When the fusion gene was expressed in murine J558L cells, we obtained soluble dimeric immunoglobulin-like proteins in the supernatant. After analyzing the function of the IL-2 and FasL portions individually in vitro, a delayed-type hypersensitivity (DTH) reaction to sheep red blood cells as model for cell-mediated immune responses was investigated to evaluate the IL-2-IgG-FasL-mediated immunosuppression in vivo.In vitro, the IL-2-IgG-FasL fusion protein supported IL-2-dependent proliferation of Fas-resistant CTLL-2 cells, whereas concanavalin A-T blasts were induced to undergo apoptosis by the FasL portion. In vivo, this fusion protein potently inhibited a murine DTH. This was associated with an increased rate of apoptosis in activated lymphocytes in the spleen, even at very low doses of the fusion protein. Furthermore, a second antigen challenge 10 days after IL-2-IgG-FasL treatment still failed to elicit a DTH response.The abrogation of a standard T cell-dependent immune response in vivo demonstrates that IL-2-IgG-FasL can be successfully exploited to trigger the death of deleterious T cells, presenting a potentially useful strategy in the management of autoimmune diseases and allotransplant rejections.

Here we provide proof that the injection of tumor cells engineered to secrete interleukin 2 (IL-2)-IgG chimeric proteins locally induces potent antitumor responses, which are more effective than tumor transfection with IL-2 alone. Murine plasmacytoma cells (J558L) were stably transfected with DNA coding for a human IL-2-IgG1 or a murine IL-2-IgG2b fusion protein and were injected s.c. into syngeneic BALB/c mice. Evaluation of tumor growth and rejection patterns showed that IL-2-IgG secretion by transfected J558L tumor cells induced their rejection in all animals tested, similar to the rejection of J558L cells engineered to secrete IL-2 alone, whereas treatment with parental cells was lethal. However, mice treated with IL-2-IgG-secreting J558L cells (human IL-2-IgG1 and murine IL-2-IgG2b) exhibited a significantly stronger tumor immunity against a later challenge with parental J558L cells than mice treated with IL-2-secreting tumor cells.

Bioelectric brain maturation of twenty infants who had suffered acute perinatal hypoxia (patients) was compared with that of twenty healthy newborns (controls). None of the patients had suffered any other pre- or perinatal complications that could have influenced the bioelectric brain maturation. All infants (postmenstrual age: 40--42 weeks) were subjected to a polygraphic recording. The patients were examined after the acute phase of their disease; all were in good clinical condition at the time of recording. Statistic evaluation revealed significantly retarded bioelectric brain maturation in the patient group. Furthermore, a more immature EEG pattern was found to correspond to greater extent of oxygen deprivation. The study shows: determination of bioelectric brain maturation can be used to obtain information about suffered hypoxia and extent of oxygen deprivation.

1. 1. Averaged evoked responses were recorded bipolarly from T5-Cz and T6-Cz in groups (I,II) of human newborns during acoustic stimulation. 2. 2. Group I was stimulated with five sounds: sine and square wave tones at 125 and 1000 c/sec, respectively, and a recorded female voice saying “baby”. Group II was stimulated with four sounds: the 125 c/sec square wave, white noise of approximately equal band width (“wide band”) and two filtered components of it (“low band” and “high band”), respectively. 3. 3. The response most consistently present following stimulation was the N2 wave. In Group I evoked N2 responses of decreasing amplitude were obtained to: the 125 c/sec square wave, the voice, the 1000 c/sec square wave, the 125 c/sec and 1000 c/sec sine waves, respectively. In Group II the order of magnitude from greatest to smallest was: 125 c/sec square wave, wide band noise, low band noise and high band noise. 4. 4. The results support the hypothesis proposed in an earlier publication, that the degree of behavioural and physiological response to sound in a newborn infant is proportional to the length of basilar membrane excited by the stimulus.

Summary In 20 healthy newborn infants a series of 14 reflexes of various modalities was studied in different behavioural states (regular sleep, irregular sleep, quiet wakefulness) and during sucking. According to our results these reflexes fall into three categories. Proprioceptive reflexes (quadriceps reflex, biceps reflex, ankle clonus and Moro reflex) show good responses during regular sleep and wakefulness, but are absent or markedly diminished in irregular sleep. Exteroceptive reflexes (plantar and palmar grasp, the Babkin reflex, the palmo-mental reflex, glabella reflex, and lip-tap reflex) are absent or diminished in regular sleep. During irregular sleep these reflexes can be elicited almost as well as during wakefulness. Nociceptive reflexes (abdominal skin reflex, the Babinski reflex and an exteroceptive skin reflex from the thigh) are equally present in the three states investigated. The magnet response could not be obtained in any of the three states. During sucking, the palmar grasp and the tendon reflexes tend to be stronger whilst the abdominal skin reflex and the exteroceptive skin reflex from the thigh are slightly weaker. The implications for the neurophysiological organization of different behavioural states in human neonates are discussed together with their consequences for the clinical neurological examination of the newborn infant.

IN a polygraphic study it was found that newborn babies responded differentially to pure and to patterned tones of equal sound pressure1. Patterned (square-wave) tones were more potent stimuli for eliciting electromyographic responses than pure (sine-wave) tones and within each of these categories those tones with low frequency fundamentals elicited most responses. Square-wave tones with low frequency fundamentals possess certain structural similarities to human speech sounds. They were therefore categorized as “supernormal” stimuli because they elicited more responses than the voice itself, which in turn was more potent than any of the sine-wave tones.

The main features of Aicardi's syndrome are infantile spasms, defects of the corpus callosum, chorioretinopathy, mental subnormality, characteristic EEG changes, vertebral anomalies, microphthalmos and colobomata. The disease affects only the female sex. 2 cases are described from our own experience.

Aberrant inflammasome priming and dysregulated secretory pathways contribute to parallel IL-18 and S100A12 hypersecretion from neutrophils in instable FMF.