Reduced number and function of peripheral dendritic cells in coeliac disease.

Dendritic cells (DC) play a pivotal role in shaping the immune response in both physiological and pathological conditions. In peripheral blood at least two subsets, the myeloid and plasmacytoid, have been described as having different T stimulatory functions and a variable degree of maturation. Certainly, antigen presentation plays a crucial role in the pathogenesis of coeliac disease and circulating immune cells are thought to reflect the state of immune response within the gut. Therefore,we aimed to investigate the quantitative and phenotypical modifications of peripheral bloodDC, together with their functional properties, in this pathological condition. Blood samples from 11 untreated patients before and after a course of gluten-free diet, 27 treated patients and 14 controls underwent flow-cytometric analysis, while immunomagnetically sorted DC from the CD patients and eight human leucocyte antigen (HLA)-DQ2/8+ bone marrow donors were used to evaluate maturation status through the CD83 expression, cytokine profile for interleukin (IL)-6, IL-10, IL-12 and interferon (IFN)-a by enzyme-linked immunosorbent assay (ELISA), and functional properties by mixed leucocyte reaction before and after pulsing with digested gliadin. We found that in both untreated and treated patients, a significant reduction of the entire DC population, mainly the plasmacytoid subset, in comparison to healthy controls was observed. In active disease, an impaired allogenic lymphocyte reaction and a significant reduction of IFN-a production, paralleled by the presence of a more immature status, were also demonstrated. All the latter modifications have been reverted by pulsing DC with digested gliadin

suPAR, a soluble form of urokinase plasminogen activator receptor, inhibits human prostate cancer cell growth and invasion

Urokinase-type plasminogen activator (uPA) and its specific membrane receptor (uPAR) control extracellular matrix proteolysis, cell migration, invasion and cell growth in several cancers. The uPAR released from human cancers is detected in blood as soluble uPAR (suPAR). No information is available on the mechanism(s) of action of suPAR on prostate cancer (PCa) cell growth and invasion. In order to clarify this issue, we tested the effect of a treatment with the human recombinant suPAR (comprising amino acids l-303) on the proliferation, migration and invasion of DU145 cells, a PCa cell line expressing a potent autocrine uPA-uPAR signalling system. The results indicate that suPAR significantly inhibits cell growth, promotes apoptosis and decreases both migration and Matrigel invasion of DU145 cells. The mechanism of action of suPAR seems to be linked to a decrease of ERK and FAK activation. Cleavage of suPAR by chymotripsin reverses these effects. When added to the uPA-negative LNCaP cells, suPAR was ineffective; on the contrary, when LNCaP cells were cultured on fibronectin-coated plates in order to stimulate uPA expression, suPAR significantly decreased cell proliferation. In conclusion, our data suggest that suPAR can function as a potent molecule scavenger for uPA in human PCa cells characterized by high levels of uPA/uPAR as in DU145 cells, while it is ineffective in uPA-deficient LNCaP cells. The molecular mechanism(s) through which suPAR participates in the control of PCa progression may bear relevance for the long-term goal to identify new therapeutic targets aimed at silencing tumours in viv

Tumor-Derived Microvesicles Induce, Expand and Up-Regulate Biological Activities of Human Regulatory T Cells (Treg)

Background: Tumor-derived microvesicles (TMV) or exosomes are present in body fluids of patients with cancer and might be involved in tumor progression. The frequency and suppressor functions of peripheral blood CD4 + CD25 high FOXP3 + Treg are higher in patients with cancer than normal controls. The hypothesis is tested that TMV contribute to induction/ expansion/and activation of human Treg. Methodology/Principal Findings: TMV isolated from supernatants of tumor cells but not normal cells induced the generation and enhanced expansion of human Treg. TMV also mediated conversion of CD4 + CD25 neg T cells into CD4 + CD25 high FOXP3 + Treg. Upon co-incubation with TMV, Treg showed an increased FasL, IL-10, TGF-b1, CTLA-4, granzyme B and perforin expression (p,0.05) and mediated stronger suppression of responder cell (RC) proliferation (p,0.01). Purified Treg were resistant to TMV-mediated apoptosis relative to other T cells. TMV also increased phospho-SMAD2/3 and phospho-STAT3 expression in Treg. Neutralizing Abs specific for TGF-b1 and/or IL-10 significantly inhibited TMV ability to expand Treg. Conclusions/Significance: This study suggests that TMV have immunoregulatory properties. They induce Treg, promote Treg expansion, up-regulate Treg suppressor function and enhance Treg resistance to apoptosis. Interactions of TMV wit

Employee Reporting in the U.K.: An Empirical Study of Managerial Objectives and Behaviour

Since the 1970's, an increase of interest was shown by researchers in employee reporting, but little empirical attention has been focused on the managerial determinants. This research addresses the need to understand how and why voluntary employee reporting developed, examining its place in the wider organisational and social context. A three-pronged enquiry was carried out in the U.K. during 1981-83, comprising documentary analysis, postal questionnaire survey and personal interviews, to find out managerial objectives and attitudes in employee communications. It traced influences from specific organisational, social and societal factors on employee reporting. Analysis of the qualitative data consistently demonstrated the importance attached by managers to reporting financial information to the employees. Their communication objectives showed a dominant social theme. Employee reporting developments result from strong faith or commitment to communications on the part of management, and their perceptions of specific pressing organisational needs and wider social and moral issues at the time. The study highlights the complexity of managers' perceptions and mixed feelings about the intrinsic value and conflicting social interests in employee information. There remains scope for experimentation on the uses and designs of employee communication systems. This research represents a contribution to the developing interpretive approach in accounting research, and to the debates about corporate accountability to the employees and public policy making

Cavernous hemangioma of the frontal bone: a case report

INTRODUCTION: Cavernous hemangiomas are rare benign bone tumors and those at the level of the cranial bones are even rarer. CASE PRESENTATION: A 50-year-old woman of Italian ethnicity presented with a frontal mass. A computed tomography scan showed an osteolytic lesion and a magnetic resonance imaging scan revealed a hypointense lesion on the T1-weighted image and a hyperintense lesion on the T2-weighted image. We performed a tailored craniectomy and cranioplasty. Histological examination revealed a cavernous hemangioma. CONCLUSIONS: These benign tumors do not have classic radiographic features and so can be misinterpreted as lesions like multiple myeloma or osteosarcoma. Consequently, the diagnosis is most often made during surgical resectio

Shedding of membrane vesicles by tumor and endothelial cells

Shedding of membrane vesicles is a vital phenomenon frequently observed in tumor cells and suggested to be involved in several aspects of tumor progression. Our previous studies have shown that human breast tumor cells rapidly shed membrane vesicles containing matrix metalloproteinases (MMPs). In this study we present that human umbilical vein endothelial cells (HUVEC) as well as different tumor cell lines (human ovarian cancer, CABA I and A2780, and hepatocarcinoma cell line, SK-Hep 1) shed vesicles in the extracellular medium. These vesicles carry MMPs and their inhibitors TIMPs. We conclude that tumor and endothelial cells shed MMP-containing vesicles and this may represent a mechanism for regulating focalized proteolytic activity and a way to interact with microenvironment during tumor angiogenesis