The cellulose synthase BcsA plays a role in interactions of Salmonella typhimurium with Acanthamoeba castellanii genotype T4

Parasitology Research - Pathogenic bacteria share their natural habitat with many other organisms such as animals, plants, insects, parasites and amoeba. Interactions between these organisms...     

The hippocampus in families with schizophrenia in relation to obstetric complications

BACKGROUND: Hippocampal volume reduction is a well replicated finding in schizophrenia. Evidence indicates a contribution of genetic and environmental factors, especially the influence of obstetric complications to this volume reduction. The aim of this study was to compare hippocampal volume of schizophrenic patients as well as and their relatives with control subjects and to quantify the additional contribution of obstetric complications. METHODS: T1 weighted MRI brain scans of 50 schizophrenic patients, 88 first-degree relatives and 53 healthy control subjects were used to perform volumetric measurements on the left and right hippocampus. A set of clinical measures including obstetric complications were recorded for all family members. RESULTS: Numerically our measurements revealed a hippocampal volume reduction in schizophrenic patients (left: - 14%, right: - 15%) and, although less pronounced, in their unaffected relatives (left: - 6%, right: - 10%). Noted differences in hippocampal volume between schizophrenic patients and controls were only significant for the left side. Hippocampal volumes of patients and their relatives with obstetric complications were reduced bilaterally. CONCLUSIONS: Hippocampal volume reduction is present in schizophrenic patients and their first-degree relatives, suggesting an influence of genetic factors.. In addition, however, obstetric complications have also been shown to play a major role.     

c-Fos-dependent induction of the small ras-related GTPase Rab11a in skin carcinogenesis

Malignant transformation of mouse skin by tumor promoters and chemical carcinogens, such as the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA), is a multistage process leading to the formation of squamous cell carcinomas. It has been shown that mice lacking the AP-1 family member c-Fos exhibit an impaired transition from benign to malignant skin tumors. Here, we demonstrate enhanced expression of the small Ras-related GTPase Rab11a after short-term TPA treatment of mouse back skin. Expression of Rab11a in vivo and in vitro critically depended on c-Fos, because TPA application to the back skin of c-Fos-deficient mice and to mouse embryonic fibroblasts did not induce Rab11a mRNA or protein expression. Moreover, dexamethasone, which is a potent inhibitor of AP-1-mediated transactivation that exhibits anti-inflammatory and anti-tumor promoting activities, inhibited TPA-induced expression of Rab11a. Within the Rab11a gene promoter, we identified a functional AP-1 binding element that exhibited elevated c-Fos binding activity after TPA treatment of keratinocytes. Enhanced expression was not restricted to chemically induced mouse skin tumors but was also found in tumor specimens derived from patients with epithelial skin tumors. These data identify Rab11a as a novel, tumor-associated c-Fos/AP-1 target and may point to an as yet unrecognized function of Rab11a in the development of skin cancer.     

Polymorphonuclear leucocytes selectively produce anti-inflammatory interleukin-1 receptor antagonist and chemokines, but fail to produce pro-inflammatory mediators

The role of neutrophils in the immune response has long been regarded as mainly phagocytic, but recent publications have indicated the production of several cytokines by polymorphonuclear leucocytes (PMN). The results of the individual reports, however, vary considerably. In this study, we established a cytokine profile of pure human neutrophils and demonstrated that minor contamination of peripheral blood mononuclear cells (PBMCs) in PMN preparations can lead to false-positive results. In our hands, peripheral blood PMN fail to produce the pro-inflammatory cytokines interleukin (IL)-1beta, IL-6 and tumour necrosis factor-alpha (TNF-alpha). Instead, they secrete large amounts of the chemokine IL-8 and the anti-inflammatory IL-1 receptor antagonist (IL-1ra). Additionally, PMN preparations of a high purity show production of the chemokines macrophage inflammatory protein (MIP)-1alpha, MIP-1beta and growth-related oncogene-alpha (GRO-alpha), as well as macrophage colony-stimulating factor (M-CSF). The neutrophil therefore represents a novelty by producing the antagonist of IL-1beta (i.e. IL-1ra) in the absence of IL-1beta itself. To support our results, we differentiated stem cells from human cord blood into PMN and monocytes, respectively. These in vitro-differentiated PMN showed the same cytokine profile as peripheral blood PMN lacking IL-1beta, while differentiated monocytes produced the expected IL-1beta in addition to IL-1ra. The clear anti-inflammatory nature of their cytokine profile enables PMN to antagonize pro-inflammatory signals in experimental conditions. It is therefore possible that PMN play a key role in immune regulation by counteracting a dysregulation of the inflammatory process. Clinical studies, in which administration of recombinant G-CSF had a favourable effect on the outcome of severe infections and even sepsis without worsening inflammation, could thus be explained by our results.     

Acute fulminant myocarditis in children and adolescents: the role of mechanical circulatory assist

We report children and adolescents in fulminant myocarditis undergoing prolonged circulatory support with different assist devices. Between 1994 and 2004, seven children and adolescents (aged 7-18 years, mean age 13.5 years) were treated with VADs (5 Thoratec, 1 Medos, 1 Novacor) for circulatory support. Three patients underwent left ventricular support; biventricular support was necessary in four patients. Four patients (three left VADs, one bi-VAD) could be successfully bridged to heart transplantation after a mean support time of 163 days (56-258 days). One 7-year-old girl (Medos-BVAD) died after a support time of 11 days because of irreversible multiorgan failure. One 18-year-old patient was successfully weaned from Thoratec BVAD after 66 days with complete recovery of left ventricular function. As good markers, atrial and brain natriuretic peptides were found which reached normal values after recovery of myocardial function. A 15-year-old girl is still on the device. In children or adolescents with irreversible shock in fulminant myocarditis with an anticipated mortality of 100%, both successful bridging to heart transplantation and successful bridging to recovery are possible. Young patients with fulminant myocarditis should be rapidly transferred to a clinic with a mechanical circulatory support program to offer this life-saving option.     

The performance of the screener to identify children with special health care needs in a European sample of children with chronic conditions

In the field of paediatric health care, measures based on consequences of health conditions have been recently developed to screen for children with special health care needs. These tools have been primarily used in survey research. The aim of this cross-sectional clinical study is to test the performance of a screener for identifying children with special health care needs (CSHCN) in a population of children with chronic conditions diagnosed and treated in different European paediatric hospitals. In the current study, the screener was employed in a sample of children with different chronic conditions (asthma, arthritis, dermatitis, epilepsy, cystic fibrosis, diabetes and cerebral palsy) across seven European countries; 456 parents of children, aged 4-7, 8-12, and 13-16 years, responded to the screener items. The study included a range of clinical measures to assess the severity of the conditions as well measures on functional health status. The prevalence of children identified positively with the CSHCN screener was 80%, which was higher than in survey estimates in the United States. Considerable variation in the screener classification was found between chronic conditions with cystic fibrosis and epilepsy showing higher rates, and skin conditions lower rates. There was no significant relationship between the screener classification and functional limitation. Findings of this study support in general the validity of the children with special health care needs screener, which shows, however, a differential validity across specific conditions. Several clinical and theoretical explanations for the lack of identifying some children with chronic conditions and the considerable variation between the conditions are discussed.Abbreviations CSHCN questionnaire for identifying children with special health care needs - FSII-(R) functional status II-(R) short form - QUICCC-R questionnaire for identifying children with special health care needs revised Funded by the European Commission, the DISABKIDS project is a cross-national effort to develop standardised instruments of health-related quality of life and needs in children and adolescents with chronic conditions. DISABKIDS international co-ordinator in chief: Monika Bullinger, Department of Medical Psychology, University Hospital of Hamburg, Martinistrasse 52, 20246 Hamburg, contract number: QLG-CT-2000-00716. Study centre: Silke Schmidt, Corinna Petersen; collaborating investigators: Hendrik Koopmann, Rolanda Baars, Department of Paediatrics, Leiden University Medical Centre, Netherlands; Peter Hoare, Hospital for Sick Children, University of Edinburgh, United Kingdom; Mick Power, Clare Atherton, Department of Psychiatry, University of Edinburgh, United Kingdom, Marie Claude Simeoni, Department of Public Health, University Hospital of Marseilles, France; John Tsanakas, Elpis Hatziagorou, Paraskevi Karagianni, University Paediatric Clinic, Athanasios Vidalis, Department of Psychiatry, Hippocratio Hospital, Thessaloniki, Greece, John Eric Chaplin, Department of Paediatrics, University Hospital Lund, Sweden; Michael Quittan, Rima Nourafza, Othmar Schuhfried, Department of Physical Medicine and Rehabilitation, University of Vienna, Austria; Ute Thyen, Esther Müller-Godeffroy, Department of Paediatrics, Medical University of Lübeck, Germany.     

Expression of selectin ligands on murine effector and IL-10-producing CD4+ T cells from non-infected and infected tissues

Endothelial selectins are crucial for the recruitment of leukocytes into sites of inflammation. On T cells, ligands for selectins become induced upon differentiation into the effector/memory stage. Initial in vitro studies suggested a correlation between the Th1 phenotype and ligand expression, but whether this also holds true in vivo remained uncertain. We here analyzed selectin ligands on CD4+ T cells producing IFN-gamma, IL-4 or IL-10, prototypic cytokines of the Th1, Th2 and Tr1 subset, respectively. We analyzed mice infected with influenza virus, the bacterium Listeria, and the parasites Toxoplasma (all Th1 models) or Nippostrongylus (Th2 model). A link between the Th1 phenotype and ligand expression was not found in vivo. Surprisingly, the potentially regulatory IL-10-producing T cells displayed the highest frequency of ligand-positive cells in general. Within the inflamed tissues, the frequencies of P-selectin-binding cells increased in the dominant subset, either Th1 or Th2. Up-regulation was also found for E-selectin ligands during influenza, but not Nippostrongylus infection. In conclusion, conditions driving T cell polarization into either Th1 or Th2 in vivo do not affect the expression of selectin ligands, but acquisition of P-selectin binding and hence migration into inflamed tissues is boosted by an inflammatory milieu.     

Progression of chronic subdural haematomas in an infant boy after abusive head trauma

Abusive head trauma is a serious form of child abuse that can lead to severe neuropsychological sequelae or death in infants. In questionable cases, without a confession from the caregivers and ambiguous clinical information, evidence for the diagnosis of abusive head trauma is often based on typical patterns that have been observed in neuro-imaging. This study shows the progressive evolution of multifocal chronic subdural haematomas, including re-bleedings, in a case of abusive head trauma in an infant boy who was documented with repeated magnetic resonance imaging. The chronic subdural haematomas occurred during closely monitored in-patient rehabilitative care, and repeated maltreatment did not appear to be likely. Due to excessive growth, neurosurgical intervention with endoscopic craniotomy, evacuation of the subdural haematomas and temporal external cerebrospinal fluid drainage was performed with a favourable recovery. This study discusses the current pathophysiological knowledge concerning the development and clinical course of chronic subdural haematomas and draws relevant conclusions for the clinical practice and psychosocial management of caring for victims of abusive head trauma.