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41.
BACKGROUND: Clinical observations indicate that patients with Alzheimer's disease show a greater susceptibility to infections. One possible explanation is that this predisposition is due to alterations in their immune system. OBJECTIVE: To investigate this assumption, pro- and anti-inflammatory cytokines, as well as the phagocytic activity and superoxide anion generation was examined in aged individuals with and without Alzheimer's disease. METHODS: The production of IL-1beta, IL-2, IL-6, TNFalpha and IL-10 by peripheral blood mononuclear cells from 12 patients with Alzheimer's disease was compared with that of 12 age-matched individuals without any signs of dementia and 12 middle-aged healthy volunteers who served as an additional control. The engulfing capacity of the phagocytic cells was detected by counting cells containing latex beads and the number of particles internalized by each individual cell. RESULTS: The secretion of IL-2 was markedly low in the demented patients, compared with both elderly and middle-aged subjects. IL-1beta and TNFalpha production was similar in the individuals of the 3 groups. The production of IL-6 and IL-10 was significantly lower when compared to that of the middle-aged, but did not differ between the elderly patients with and without dementia. The phagocytic function of both polymorphonuclear cells and monocytes was decreased in individuals of the elderly groups with a low number of engulfed latex particles by each individual polymorphonuclear cell. The production of superoxide anions was increased only by monocytes from the elderly groups. CONCLUSIONS: The results suggest that although the impaired immune function in patients with Alzheimer's disease is related to the aging process, the significant low IL-2 production in these patients may play a role in their increased susceptibility to infections. 相似文献
42.
Molecular imaging allows the non-invasive assessment of membrane transporter expression and function in living subjects. Such technologies have the potential to become diagnostic and prognostic tools, allowing detection, localization, and prediction of response of tumors and their metastases to therapy. Beyond tumors, imaging can also help understand the role of transporters in adverse drug effects and drug clearance. Here, we review molecular imaging technologies that monitor transporter-mediated processes. We emphasize emerging probe substrates and potential clinical applications of imaging the function of membrane transporters in cancer.KEY WORDS: membrane transporters, molecular imaging, multidrug resistance, near infrared, optical imaging 相似文献
43.
William Dunlop Lachlan Hegarty Margaret Staples Michele Levinson Michael Ben‐Meir Katherine Walker 《Emergency medicine Australasia : EMA》2018,30(1):61-66
Objective
We aimed to evaluate patient perceptions of medical scribes in the ED and to test for scribe impacts on ED Net Promoter Scores, Press Ganey Surveys and other patient‐centred topics.Methods
Exploratory semi‐structured interviews were conducted in the ED during wait times after scribed consultations. Interview results were used to derive topics relating to scribes. Items addressing these topics from validated surveys were combined with items from widely used patient satisfaction questionnaires. Questionnaires were administered in the ED by face‐to‐face approach while patients were waiting for admission/discharge or test results. Patients and doctors were blinded to the purpose of the questionnaire. The survey evaluated for non‐inferiority of scribed consultations, using Net Promoter Scores, Press Ganey questions and questions specific to the presence of the scribe.Results
Patient interviews did not identify any negative views regarding the presence of scribes during consultations. Thematic saturation was achieved after seven interviews. Two hundred and fifty‐eight patients were approached to complete the questionnaire, and 215 participated (83%); 95 and 118 participants in the scribed and non‐scribed groups, respectively. There was no difference between scribed and non‐scribed consultations on the following measures of satisfaction: the Net Promoter Score, Press Ganey questions, quality of information received from doctors, communication, privacy concerns or inhibition about revealing private information and room crowding.Conclusion
We found no evidence that scribes reduce patient satisfaction during emergency consultations, nor prompt discomfort that might cause a patient to withhold information. 相似文献44.
Dimitrios P. Bogdanos Daniel S. Smyk Pietro Invernizzi Eirini I. Rigopoulou Miri Blank Lazaros Sakkas Shideh Pouria Yehuda Shoenfeld 《Immunologic research》2013,56(2-3):220-240
We recently introduced the concept of the infectome as a means of studying all infectious factors which contribute to the development of autoimmune disease. It forms the infectious part of the exposome, which collates all environmental factors contributing to the development of disease and studies the sum total of burden which leads to the loss of adaptive mechanisms in the body. These studies complement genome-wide association studies, which establish the genetic predisposition to disease. The infectome is a component which spans the whole life and may begin at the earliest stages right up to the time when the first symptoms manifest, and may thus contribute to the understanding of the pathogenesis of autoimmunity at the prodromal/asymptomatic stages. We provide practical examples and research tools as to how we can investigate disease-specific infectomes, using laboratory approaches employed from projects studying the “immunome” and “microbiome”. It is envisioned that an understanding of the infectome and the environmental factors that affect it will allow for earlier patient-specific intervention by clinicians, through the possible treatment of infectious agents as well as other compounding factors, and hence slowing or preventing disease development. 相似文献
45.
Carlo Perricone Nancy Agmon-Levin Fulvia Ceccarelli Guido Valesini Juan-Manuel Anaya Yehuda Shoenfeld 《Immunologic research》2013,56(2-3):206-219
Autoimmune diseases (ADs) are chronic conditions initiated by the loss of immunological tolerance to self-antigens. The pathogenic hypothesis comprises a complex interaction between genetic, environmental and hormonal factors that interact with an individual over time generating a dysregulation of the immune system leading to disease development. Several polymorphic genes contribute to the development of ADs. Furthermore, age and gender play a major role by influencing hormone levels that can represent the fulcrum unbalancing from susceptibility to protection. Evidences suggest that while all these steps occur, the susceptible individual develops autoantibodies over a long time lapse. Such autoantibody production is genetically determined and finally, their presence seems to determine the clinical presentation of ADs. The genetic predisposition to the developments of autoantibodies and toward the disease process may overlap. The unveiling of these mechanisms could allow not only to treat but also to prevent the development of autoimmune diseases. 相似文献
46.
Svetlana Fischer Nancy Agmon-Levin Yinon Shapira Bat-Sheva Porat Katz Eduard Graell Ricard Cervera Ljudmila Stojanovich Jose A. Gómez Puerta Raimon Sanmartí Yehuda Shoenfeld 《Immunologic research》2013,56(2-3):287-292
Parasitic infections may induce variable immunomodulatory effects and control of autoimmune disease. Toxoplasma gondii (T. gondii) is a ubiquitous intracellular protozoan that was recently associated with autoimmunity. This study was undertaken to investigate the seroprevalence and clinical correlation of anti-T. gondii antibodies in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). We evaluated sera from European patients with RA (n = 125) and SLE (n = 164) for the prevalence of anti-T. gondii IgG antibodies (ATXAb), as well as other common infections such as Cytomegalovirus, Epstein-Barr, and Rubella virus. The rates of seropositivity were determined utilizing the LIAISON chemiluminescent immunoassays (DiaSorin, Italy). Our results showed a higher seroprevalence of ATXAb in RA patients, as compared with SLE patients [63 vs. 36 %, respectively (p = 0.01)]. The rates of seropositivity of IgG against other infectious agents were comparable between RA and SLE patients. ATXAb-seropositivity was associated with older age of RA patients, although it did not correlate with RA disease activity and other manifestations of the disease. In conclusion, our data suggest a possible link between exposure to T. gondii infection and RA. 相似文献
47.
Intravenous immunoglobulin (IVIg) is used to treat a number of immune-deficiencies and autoimmune diseases. It has been shown that IVIg contains anti-idiotypic antibodies, which explains its immunomodulatory action.In murine models, recent investigations have demonstrated that IVIg can prevent and reduce the affliction by systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS) and scleroderma. Relevant disease-specific fractions of IVIg were able to reproduce and even enhance the therapeutic effect in a murine model.IVIg treatment before tumor resection in rodents inoculated with melanoma and sarcoma cells dramatically improved the cure rate (50%) in comparison to the control group (0%).In patients affected by SLE, several clinical manifestations responded to IVIg treatment including serositis, hematological manifestations, treatment-resistant nephritis and central nervous system involvement. Similarly, in women with recurrent fetal loss due to APS, IVIg was able to diminish the abortion rate. Vasculitides such as Churg–Strauss' and Wegener's and skin fibrosis in patients affected by scleroderma improved after IVIg treatment. In agreement with in vitro investigations, prolonged survival has been noted in cancer patients treated with IVIg.We suggest that in the presence of a steroid and immunosuppressive-resistant autoimmune disease, IVIg is a rational and safe choice. 相似文献
48.
Gisele Zandman-Goddard Yehuda Shoenfeld Gisele Zandman-Goddard Yehuda Shoenfeld 《Autoimmunity》2013,46(7):473-485
Viral and bacterial infections may serve as an environmental trigger for the development or exacerbation of systemic lupus erythematosus (SLE) in the genetically predetermined individual. In addition, SLE patients are more prone to develop common (pneumonia, urinary tract infection, cellulitis, sepsis), chronic (tuberculosis), and opportunistic infections possibly due to inherit genetic and immunologic defects (complement deficiencies, mannose-binding lectin [MBL] polymorphisms, elevated Fcgamma III and GM-CSF levels, osteopontion polymorphism), but also due to the broad spectrum immunosuppressive agents that are part of therapy for severe manifestations of the disease. Hence, SLE patients are considered a high-risk population, where identification and treatment of chronic infections such as tuberculosis, hepatitis B or human immunodeficiency virus, are important prior to the institution of immunosuppression so as to prevent reactivation or exacerbation of the infection. Infections in SLE patients remain a source of morbidity and mortality. A caveat often encountered is to distinguish between a lupus flare and an acute infection; in such cases parameters including elevated CRP (and adhesion molecules) may aid in the diagnosis of infection. Recent research has provided convincing evidence that EBV infection may play a major role not only in molecular mimicry but also in aberrations of B cells and apoptosis leading to a state of perpetual heightened immune response in SLE. 相似文献
49.
Udi?Nussinovitch Yehuda?ShoenfeldEmail author 《Clinical reviews in allergy & immunology》2013,44(1):98-108
Autoimmunity is influenced by genetic, immune, hormonal, and environmental factors. Viral infections may trigger autoimmunity. It has been established that autoimmunity may be a contributing factor in the pathogenesis of heart disease. Anti-heart autoantibodies have been identified in the sera of patients with heart diseases, as well as in low titers in certain healthy individuals. Nevertheless, the role of humoral immunity in the development of autoimmune heart disease has not been fully established. Anti-myosin autoantibodies appear in several heart diseases such as myocarditis, dilated cardiomyopathy, Chagas' heart disease, Kawasaki disease, rheumatic fever, and ischemic myocardium. The pathogenic role of anti-myosin autoantibodies in heart disease is not fully understood. Moreover, little is known concerning the clinical implications of anti-myosin autoantibodies in heart disease and its prognostic significance. Anti-cardiac myosin autoantibodies were found to cross-react with the β-adrenergic receptor. Studies have reported the effective use of the anti-myosin directed immune-modulating approach in animals with heart disease, although no specific anti-myosin autoantibody therapeutic approach has been attempted in humans. Herein, we review the current knowledge of anti-myosin autoantibodies and the use of targeted immune-modulating therapy in different heart diseases. 相似文献
50.
Gisele Zandman-Goddard Hedi Orbach Nancy Agmon-Levin Mona Boaz Howard Amital Zoltan Szekanecz Gabriella Szucs Josef Rovensky Emese Kiss Nadia Corocher Andrea Doria Ljudmila Stojanovich Francesca Ingegnoli Pier Luigi Meroni Blaz Rozman Jesus Gomez-Arbesu Miri Blank Yehuda Shoenfeld 《Clinical reviews in allergy & immunology》2013,44(1):23-30
Ferritin may play a direct role on the immune system. We sought to determine if elevated levels of ferritin in lupus patients correlate with disease activity and organ involvement in a large cohort. Ferritin levels (gender and age adjusted) were assessed in 274 lupus serum samples utilizing the LIASON Ferritin automated immunoassay method. Significant disease activity was determined if European Consensus Lupus Activity Index (ECLAM)?>?2 or Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)?>?4. Utilizing an EXCEL database, we compared elevated ferritin levels to manifestations grouped by organ involvement, serology, and previous therapy. The patients were predominantly female (89%), median age was 37 years old, and disease duration was 10.6?±?7.7 years. Hyperferritinemia was found in 18.6% of SLE patients. Compared to subjects with normal ferritin levels, a significantly greater proportion of patients with hyperferritinemia had thrombocytopenia (15.4% vs. 33.3%, p?=?0.003) and lupus anticoagulant (11.3% vs. 29.0%, p?=?0.01). Additionally, compared to normoferritinemic subjects, hyperferritinemic subjects had significantly higher total aCL (99.7?±?369 vs. 30.9?±?17.3 GPI, p?=?0.02) and aCL IgM antibody levels (75.3?±?357.4 vs. 9.3?±?10.3 GPI, p?=?0.02), and marginally lower aCL IgG antibody levels (9.2?±?4.9 vs. 9.7?±?3.9 GPI, p?=?0.096). While the ECLAM score significantly correlated with hyperferritinemia (p?=?0.04), the SLEDAI score was marginally associated with hyperferritinemia (p?=?0.1). Serositis was marginally associated with hyperferritinemia, but not with other manifestations. An association with serologic APS was encountered. Hyperferritinemia was associated with thrombocytopenia, lupus anticoagulant, and anti-cardiolipin antibodies suggest that it may be an early marker for secondary antiphospholipid syndrome in SLE patients. 相似文献