1,721,158 research outputs found

    Immunotoxicology in occupational and environmental health: Perspectives, restraints and aims of research

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    The immune system is able to recognize and neutralize potentially harmful agents, conferring to the organism resistance to infections and malignant diseases. The authors have reviewed the literature and identified a group of substances able to enhance and/or reduce different immune functions, both in an experimental model and in occupational and environmental human exposure. The group includes several polyhalogenated hydrocarbons, particularly polychlorinated biphenyls, polybrominated biphenyls, tetrachloro-dibenzo-p-dioxin (TCDD), some metals like lead, cadmium and mercury, pesticides, i.e. dithiocarbamates and organotin compounds, organic solvents. The observed changes are usually slight and do not allow prognostic conclusion. In this study, the authors propose a 3-level rank of tests suitable for the immune evaluation of individuals occupationally exposed to xenobiotics, divided into three levels, as follows: tier 1: immunoglobulin classes (IgG, IgA, IgM), complement fractions (C3, C4), rheumatoid factor, and non-organ specific autoantibodies (AMA, SMA, ANA); CD3, CD4, CD8, CD57, CD20, HLA-DR; CD3/HLA-DR positive lymphocyte subsets; tier 2: determination of the mitotic response of peripheral blood lymphocytes to phytohaemoagglutinin, anti-CD3 monoclonal antibody, phorbol-myristate- acetate (PMA) and polyclonal immunoglobulin production after stimulation with pokeweed mitogen; tier 3: cytokine production with and without mitogen stimulation. The approach is 'step by step' and assumes the need of a closely integrated and comparative evaluation of the findings obtained. The protocol could be used in research fields; moreover, some of the tests could be useful in the monitoring of persons exposed in the environment or in the workplace to immunotoxic substances or to biological agents

    Age-related changes of Beta-Endorphin and Cholecystokinin in human and rat mononuclear cells

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    Beta-endorphin (BE) and cholecystokinin (CCK) were measured in fresh PBMC isolated from human subjects and rats. The BE and CCK PBMC contents increased significantly with age both in human and rat models. Moreover, polyclonal stimulation induced a significant decrease of BE but not CCK contents in mononuclear cells from human aged subjects. The time course of changes in BE and CCK concentrations observed in fresh and cultured cells from subjects of different ages did not directly correlate to the time course of age-associated impairment of lectin-induced lymphocyte proliferative response and interleukin-2 synthesis. In fact, the lymphocyte functional defects were significantly observed only in the 71-99 year age group, whereas the neuropeptide changes were already evident in the 31-50 age group. Since BE has been shown to participate in the modulation of the immune system, the age-related modifications of PBMC BE could play a role in the immunodepression observed during aging

    Immune parameters in biological monitoring of pesticide exposure: Current knowledge and perspectives

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    Exposure to pesticides can cause a number of effects on the immune system, varying from a slight modulation of immune functions to the development of clinical immune diseases. The aim of this study has been reviewing published data on immune effects of pesticides in humans, with particular attention for effects observed in absence of any other change, and to the possibility of identifying a dose effect relationship. Some evidence of immunotoxic effects in man involve organophosphorus compounds, some organochlorine insecticides (OC), some carbamates, some phenoxy herbicides, dithiocarbamates, and pentachlorophenol (PCP). The alterations are usually observed in absence of any other change; in some cases, data suggest the presence of a dose effect relationship. The prognostic significance of the observed changes is still unclear. The Authors propose a tier approach to assess immune effects in humans

    OH vitamin D down-regulates in vitro production of antierithrocyte antibodies in autoimmune haemolytic anaemia

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    Background: Vitamin D is a well known regulator of bone and calcium balance that has multiple immune-modulating activities. Reduced levels of 25-OH vitamin D have been found in various autoimmune diseases, such as systemic lupus systemic lupus erythematous and multiple sclerosis, and its levels and supplementation did correlate with disease clinical severity. Aims: We evaluated a) the effect of vitamin D on the in vitro production of antiRBC autoantibodies in patients with autoimmune haemolytic anaemia (AIHA); b) vitamin D levels, VDR expression and immunemodulatory cytokines. Methods: Clinical and haematological parameters, serum samples and informed consent were collected at the time of enrolment from January 2013. 25-OH vitamin D levels, VDR and IL-6, IL-10, IL-17, TNF-alfa and IFN-gamma were evaluated in 40 patients and in 40 age and sex matched healthy controls, using ELISA kits. Heparinized blood samples from 7 AIHA patients were tested for anti-RBC production in unstimulated and PWM-stimulated 48h cultures with or without vitamin D at increasing concentrations (10, 20 and 40 ng/mL). The number of immunosuppressive therapy lines (steroids, immunosuppressors, rituximab, splenectomy) were retrospectively collected. Results: Laboratory features of the patients (15 males and 25 females; mean age 58 years; 18 CAD, 18 WAIHA and 4 DAT negative AIHA) are shown in Figure 1a. Vitamin D levels were significantly reduced in patients versus controls, regardless sex, age nor season at sampling. VDR was increased in patients compared to controls; IL-6, IL-10, IL-17 and IFN-gamma serum levels were reduced. As shown in Figure 1b, vitamin D (at 10, 20, and 40 ng/mL) exerted a dose dependent inhibition on in vitro production of anti-RBC antibodies, with a delta% reduction of 6, 16 and 31 in unstimulated conditions, and 2, 1, 16 in PWM-stimulated conditions, respectively. As regards treatment at sampling, 24 patients were under low dose steroids (e.g. 0,2-0,5 mg/Kg/day prednisone); vitamin D status was comparable in treated and untreated cases. Retrospectively, 2 cases were therapy naïve, 13 cases had been treated with steroid only, 15 cases with both steroid and a second line treatment (9 rituximab and 4 cyclophosphamyde), and 10 with more than 2 lines of therapy (4 splenectomy, 10 rituximab and 6 cyclophosphamyde). Vitamin D levels were significantly lower in patients who had been treated with 2 or more lines of therapy (1,72±1 versus 2,78±2 ng/mL, p=0.04). Summary and Conclusions: Vitamin D deficiency/insufficiency was observed in patients with AIHA, both therapy naive or previously treated, with concomitant alteration of immuno-modulatory cytokine levels. Moreover, we found increased VDR expression, possibly reflecting an up-regulation due to ligand deficiency or increased shedding because of reduced receptor recruitment. Vitamin D deficiency was more evident in relapsed/refractory patients, suggesting a more pronounced immune disregulation in these cases. In vitro studies demonstrated a dose dependent inhibitory effect of vitamin D on the production of anti-RBC auto-antibodies even at very low concentrations and suggested that vitamin D supplementation may be useful in AIHA

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis

    Chronic benign neutropenia in adults: laboratory and clinical parameters of a 6-year follow-up

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    Background: Chronic benign neutropenia (CBN) is a rare hematological condition, characterized by an absolute neutrophil counts (ANCs) lower than 1800/μl in white and 1500/μl in black people for more than 3 months. This condition can be congenital or acquired, idiopathic or secondary and may be characterized by the presence of anti-neutrophils antibodies. While congenital and acquired forms of infancy and childhood are largely studied, with particular attention to the infective diathesis, less is known about adult neutropenia. Aims: To evaluate clinical and laboratory features of chronic benign neutropenia in adult patients, focusing on ANCs variations, on the positivity for anti-neutrophil auto-antibodies and on the incidence of infectious episodes. Methods: Complete blood counts and physical examination were performed every 3-4 months in the first 2 years, then at least once a year. Anti-neutrophil antibodies were determined by direct and indirect granulocyte immunofluorescence test (GIFT method). Infectious episodes were defined according to Common Terminology Criteria for Adverse Events (Version 4.0 http://evs.nci. nih.gov). Results: 47 patients (17 males and 30 females, median age 55 years, range 25- 86 years) were followed up for a median time of 47 months (range 6-240 months). As Figure 1 shows, mean ANCs at enrolment and over time displayed a great variability, both inter and intra-subject (>500/μl in 74% and >1000/μl in 25% of patients). Considering the severity of neutropenia, we observed 23 patients (49%) with neutrophils lower than 1000/μl in at least one observation (median number of 470/μl neutrophils, range 100-969/μl). Finally, the mean ANCs observed during the follow up was significantly lower in males than in females (610/μl, range 100-1380/μl versus 1070/μl, range 100-1750/μl, respectively; P=0,02). Anti-neutrophil antibodies were detected in 18/45 patients (40%), and mean ANCs were significantly lower in positive versus negative cases (P=0,021 for 6 and 12 months time). Bone marrow evaluation showed features of dismyelopoiesis in 14 cases (56%), hypocellularity in 3 (12%) and normal morphology in 8 (32%). Flow cytometry demonstrated increased Natural Killer cells in 13 patients (28%), Cytogenetic was normal 22 cases (88%), while in 3 male patients karyotype was 45, X0 (7,6 and 3 metaphases respectively). Finally, monocyte counts were higher than 600/μl in 8 patients (17%), and 5 of them (62%) showed an NK marrow infiltrate (P=0,015). Mild splenomegaly was present in 10 patients (21%) with a mean maximal diameter of11,4 cm by ultrasonography. These cases displayed lower ANCs compared with cases without splenomegaly (835/μl, 140-1400, versus 1380/μl, 200-3239, at 3 months; P=0,03). During the study 11 patients (23%) had an infection needing oral antibiotic or antiviral therapy (7 upper respiratory tract infections, 3 Herpes Zoster Virus infections and 1 urinary tract infection); no relationship was found between the occurrence of infections and the patient’s mean ANCs value, the nadir of ANCs, and the presence of anti-neutrophil antibodies Summary and Conclusions: In spite of the alarm that produces in the general practitioner, CBN in adults is a benign disease, often incidentally diagnosed, with an infectious rate comparable to that of general population and frequent spontaneous ANCs variations. Bone marrow evaluation shows abnormal findings in a half of patients, without reaching the criteria for clonal hematological diseases, but suggesting that this condition deserves clinical follow up
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