Origin and filiation of human plasmacytoid dendritic cells

Human plasmacytoid dendritic cells represent a rare population of leukocytes which produce high amounts of type I interferon in response to certain viruses. Although those cells were first described in 1958, there are still unsolved issues related to their origin and function. Recently, a leukemic counterpart of plasmacytoid dendritic cells was identified. Molecular approaches using either normal or leukemic plasmacytoid dendritic cells provide some new insights into the controversial lymphoid origin of those cells. The need for specific markers is still a critical aspect for the identification of plasmacytoid dendritic cells, whatever stage of differentiation, in normal as well as in pathological conditions. Hopefully, novel markers will allow delineation of the relationships between dendritic cells at different stages of differentiation/maturation along the myeloid and lymphoid lineages.     

The phosphatidylinositol 3-kinase/protein kinase B signaling pathway is activated by lipoteichoic acid and plays a role in Kupffer cell production of interleukin-6 (IL-6) and IL-10

Sepsis caused by gram-positive bacteria lacking lipopolysaccharide (LPS) has become a major and increasing cause of mortality in intensive-care units. We have recently demonstrated that the gram-positive-specific bacterial cell wall component lipoteichoic acid (LTA) stimulates the release of the proinflammatory cytokines in Kupffer cells in culture. In the present study, we have started to assess the signal transduction events by which LTA induces the production of tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), and the anti-inflammatory cytokine IL-10 in rat Kupffer cells. LTA was found to trigger phosphorylation of mitogen-activated protein kinases (MAPK) (p38 MAPK and ERK 1/2) and protein kinase B (PKB). Compared to LPS, LTA was more potent in inducing PKB phosphorylation after 40 min, although we found that the cytokine responses were similar. For both bacterial molecules, blocking phosphatidylinositol 3-kinase (PI3-K; Ly294002) or Janus kinase 2 (JAK-2; AG490) particularly affected the induction of IL-6 and IL-10 release, whereas TNF-alpha levels were strongly reduced by inhibition of Src family tyrosine kinases (PP2). All three cytokines were reduced by inhibition of p38 MAPK (SB202190) or the broad-range tyrosine kinase inhibitor genistein, whereas IL-6 release was particularly blocked by inhibition of ERK 1/2 (PD98059). Divergences in the regulatory pathways controlling TNF-alpha, IL-10, and IL-6 production in Kupffer cells following LPS or LTA stimulation may create a basis for understanding how the balance between pro- and anti-inflammatory cytokines is regulated in the liver following infections by gram-positive or gram-negative bacteria.     

Analysis of cytogenetic aberrations in esthesioneuroblastomas by comparative genomic hybridization

Esthesioneuroblastoma (ENB) are rare tumors originating from the olfactory epithelium of the superior nasal cavity. This lesion is morphologically closely related to Ewing sarcoma and other peripheral primitive neuroectodermal tumors (pPNET). The affiliation of ENB to the pPNET family is still under discussion. Only very limited and contradictory cytogenetic data are available on ENB and only one patient has been analyzed by comparative genomic hybridization (CGH), so far. In the present study, genomic imbalances of three ENB were analyzed by CGH to evaluate (1) a recurrent pattern of imbalances, and (2) its relation to the pPNET family. The CGH analysis of three ENB revealed multiple recurrent aberrations including DNA overrepresentations of chromosomal material of the entire chromosome 19, partial gains of the long arms of chromosomes 8, 15, and 22, and deletions of the entire long arm of chromosome 4. Beside these common aberrations, several single gains and losses occurred, that is, gains on 6p, 10q, 1p, 9q, and 13q. We confirmed the former observation of amplified genetic material on chromosome 8 and found several new, currently not described recurrent genetic aberrations distinct from those described for pPNET. Our findings give evidence that ENB is not part of the pPNET family. We suggest that the combined gain of genetic material on 15q, 22q, and chromosome 8 might be indicative for ENB. To verify our findings and to define prognosis-related aberrations, a larger number of cases needs to be studied.     

Isolation and identification of pathogenic Acanthamoeba strains in Tenerife, Canary Islands, Spain from water sources

A comprehensive survey to document the presence of free-living amoebae of the genus Acanthamoeba was conducted in tap water and sea water sources related to human environments in Tenerife, Canary Islands, Spain. Acanthamoeba identification was based on the morphology of cyst and trophozoite forms and PCR amplification with a genus-specific primer pair. The pathogenic potential of Acanthamoeba isolates was characterized by temperature and osmotolerance assays and PCR reactions with two primer pairs related to Acanthamoeba pathogenesis. The results demonstrate the presence of potentially pathogenic strains in both sources. Thus, some of the amoebae in these aquatic habitats can act as opportunistic pathogens, could play a role in the diseases of aquatic organisms, and may present a risk to human health.     

Comparison of GB virus C, HIV, and HCV infection markers in hemophiliacs exposed to non-inactivated or inactivated factor concentrates.

BACKGROUND: Until the mandatory introduction of viral inactivation techniques of blood plasma products in the early 1980s many recipients of these products were infected with various viral pathogens. OBJECTIVES: To determine the rate of transmission of GB virus C/hepatitis G virus (GBV-C/HGV) HCV, and HIV through non-virus-inactivated clotting factor concentrates in hemophiliacs, as well as the relation between amount of administered clotting factor and risk for GBV-C/HGV infection. STUDY DESIGN: In this cross-sectional study, we determined retrospectively the rates of infection markers for GBV-C/HGV, HCV, and HIV in a German cohort of hemophiliacs treated with documented amounts of non-virus-inactivated clotting factor concentrates (group A) and in a second group of hemophiliacs who were treated exclusively with virus-inactivated clotting factor (group B). The presence of anti-virus antibodies was determined by ELISA. Viral RNA was detected by RT-PCR. Markers for viral infections were compared to amounts of administered non-virus-inactivated clotting factor. RESULTS: Among hemophiliacs treated with documented amounts of non-virus-inactivated clotting factor the prevalence for GBV-C/HGV, HCV, and HIV was 40.3%, 98.6%, and 56.3%, respectively. In contrast to HIV, the rate of GBV-C/HGV infections did not increase with increasing amounts of consumed non-inactivated clotting factor. Even in the subgroup of heavily treated hemophiliacs the rate of GBV-C/HGV infection markers did not exceed 45%. CONCLUSIONS: The amount of non-virus-inactivated clotting factor is not predictive for the risk of GBV-C/HGV infection in hemophiliacs. Despite repeated parenteral exposure more than 55% of hemophiliacs were not infected with GBV-C/HGV. Our findings indicate a high frequency of host factors preventing parenteral transmission of GBV-C/HGV.     

T cell reactivity in neonates from an East and a West German city--results of the LISA study

BACKGROUND: Within an ongoing birth cohort study (LISA) the cytokine production of cord blood T cells was compared between neonates from Leipzig (East Germany) and Munich (West Germany). The aim of this study was to analyse regional differences and influencing factors of the immune status. METHODS: Cytokine production was measured in a randomly selected subgroup of 158 children from the LISA (Life style - Immune system - Allergy) cohort by intracellular cytokine staining. Information on family "atopy" history (FAH) and home characteristics was obtained from questionnaires. RESULTS: Reduced numbers of interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) producing T cells were found in association with biparental FAH and housing renovation during pregnancy. In addition, cytokine production was influenced by season. In Munich, the frequency of biparental FAH and of renovation measures during pregnancy was significantly higher as compared to Leipzig. Neonates from Munich showed significantly decreased amounts of IFN-gamma and TNF-alpha and elevated levels of interleukin-4 (IL-4) producing T cells. Differences in cytokine production between Munich and Leipzig were influenced by season (IL-4) and housing renovation (IFN-gamma, TNF-alpha). CONCLUSIONS: Since differences in the T cell cytokine production of neonates in Munich and Leipzig are independent from FAH our findings may provide evidence for the impact of environmental factors upon the fetal immune system.     

Suppressed Cell-Mediated Immunity and Monocyte and Natural Killer Cell Activity Following Allogeneic Immunization of Women with Spontaneous Recurrent Abortion

Spontaneous recurrent abortion (SRA) has been treated by means of immunization with paternal or third-party white blood cells, yet the immunological basis for SRA and for the role of immunization protocols in pregnancy outcome remains controversial. To elucidate this question, nine women with SRA were immunized with paternal mononuclear cells and studied before and 2 weeks after immunization. Seven women who became pregnant gave birth to live newborns. Secretion of the T helper 1 cytokines IL-2 and interferon- by patients' mononuclear cells decreased, while production of IL-10 increased. The levels of natural killer and lymphokine-activated killer cell-mediated cytotoxicity were markedly decreased. Monocyte functions such as secretion of IL-l, tumor necrosis factor a, IL-6, and cytotoxic activity decreased concurrently with elevations in IL-10 and transforming growth factor secretion. Production of IL-12, a pivotal regulatory cytokine, decreased. Furthermore, B7/1 expression on patients' mononuclear cells was downregulated. This resulted in a decrease in monocyte costimulatory activity of purified T cells with soluble anti-CD3, paralleled by a decline in allogeneic proliferative responses. These results suggest that the improved pregnancy success rate in women with SRA following immunization may be partly related to suppression of cell-mediated immunity and monocyte and natural killer cell activity.     

Attempted suicide in west London, II. Inter-group comparisons

BACKGROUND: Previous studies of attempted suicide have suggested that cultural and social factors play a significant role in the causation of deliberate self-harm. METHOD: In order to measure elements of culture conflict two inter-group comparisons were undertaken. In the first, 27 Asian women who had presented to hospital services following attempted suicide (Asian group) were matched with a group of similar age Asian women attending GP surgeries for other reasons (Asian GP attenders group). The second comparison was between the Asian and 46 White attempters. RESULTS: On comparing Asian attempters with Asian GP attenders group the former were more likely to have a history of previous suicidal behaviour, to have a psychiatric diagnosis, and be unemployed. Their parents were more likely to have arrived in the United Kingdom at an older age. In addition, those who attempted suicide were more likely to have been in an inter-racial relationship and to have changed religions. In the second inter-group comparison, the characteristics of Asian and White suicide attempt patients were examined. White attempters were more likely to have mental illness, and were more likely to use alcohol as part of the method of attempted suicide. By contrast, Asian attempters had experienced life events pertaining to relationships, took fewer tablets and yet expressed greater regret at not succeeding in the attempt. CONCLUSIONS: Although numbers are small, social stress and other cultural factors play an important role in the act of deliberate self-harm.