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This paper studies an (n+4)‐dimensional nonlinear virus dynamics model that characterizes the interactions of the viruses, susceptible host cells, n‐stages of infected cells, B cells and cytotoxic T lymphocyte (CTL) cells. Both viral and cellular infections have been incorporated into the model. The infected‐susceptible and virus‐susceptible infection rates as well as the generation and removal rates of all compartments are described by general nonlinear functions. Five threshold parameters are computed, which insure the existence of the equilibria of the model under consideration. A set of conditions on the general functions has been established, which is sufficient to investigate the global dynamics of the model. The global asymptotic stability of all equilibria is proven by utilizing Lyapunov function and LaSalle's invariance principle. The theoretical results are illustrated by numerical simulations of the model with specific forms of the general functions. [ABSTRACT FROM AUTHOR]

Aims: Agonistic antibodies against neurohumoral receptors can induce cardio‐noxious effects by altering the baseline receptor activity. To estimate the prevalence of autoantibodies directed against the beta‐1 receptor (b1‐AAB) in patients admitted to the hospital for acute heart failure (HF) at (i) baseline and (ii) after 6 months of follow‐up (F6) and (iii) after another 12 months of follow‐up (i.e. 18 months after index hospitalization), to estimate their prognostic impact on clinical outcome (death or first hospitalization for HF). Methods and results: In 47 patients, b1‐AAB were serially determined in serum samples collected at index hospitalization and at 6 months of follow‐up (F6) with a flow cytometry‐based assay: median age 71 years (quartiles 60, 80), 23 (49%) women, 24 (51%) HF with preserved ejection fraction. Beta1‐AAB were detected in three subjects at index hospitalization (6%), and in eight subjects at F6 (17%). There were no differences apparent between patients with and without b1‐AAB at F6 with regard to age, sex, type, duration, or main cause of HF. During the 12 month period following F6 (i.e. up to month 18), eight events occurred. Event‐free survival was associated with prevalence of b1‐AAB at F6. Compared with patients without b1‐AAB at F6, age‐adjusted Cox regression indicated a higher event risk in patients harbouring b1‐AAB, with a hazard ratio of 8.96 (95% confidence interval 1.81–44.50, P = 0.007). Conclusions: Our results suggest a possible adverse prognostic relevance of b1‐AAB in patients with acute HF, but this observation needs to be confirmed in larger patient collectives. [ABSTRACT FROM AUTHOR]

Aims: It has been hypothesized that cardiac decompensation accompanying acute heart failure (AHF) episodes generates a pro‐inflammatory environment boosting an adaptive immune response against myocardial antigens, thus contributing to progression of heart failure (HF) and poor prognosis. We assessed the prevalence of anti‐myocardial autoantibodies (AMyA) as biomarkers reflecting adaptive immune responses in patients admitted to the hospital for AHF, followed the change in AMyA titres for 6 months after discharge, and evaluated their prognostic utility. Methods and results: AMyA were determined in n = 47 patients, median age 71 (quartiles 60; 80) years, 23 (49%) female, and 24 (51%) with HF with preserved ejection fraction, from blood collected at baseline (time point of hospitalization) and at 6 month follow‐up (visit F6). Patients were followed for 18 months (visit F18). The prevalence of AMyA increased from baseline (n = 21, 45%) to F6 (n = 36, 77%; P < 0.001). At F6, the prevalence of AMyA was higher in patients with HF with preserved ejection fraction (n = 21, 88%) compared with patients with reduced ejection fraction (n = 14, 61%; P = 0.036). During the subsequent 12 months after F6, that is up to F18, patients with newly developed AMyA at F6 had a higher risk for the combined endpoint of death or rehospitalization for HF (hazard ratio 4.79, 95% confidence interval 1.13–20.21; P = 0.033) compared with patients with persistent or without AMyA at F6. Conclusions: Our results support the hypothesis that AHF may induce patterns of adaptive immune responses. More studies in larger populations and well‐defined patient subgroups are needed to further clarify the role of the adaptive immune system in HF progression. [ABSTRACT FROM AUTHOR]

We incorporate three distributed time delays into the model of pathogen dynamics with antibody and Cytotoxic T Lymphocyte (CTL) immune responses. We consider both actively and latently infected cells. The pathogen‐target incidence rate, production/proliferation, and removal rates of the cells and pathogens are represented by general nonlinear functions. We show that the solutions of the proposed model are nonnegative and ultimately bounded. We derive four threshold parameters that fully determine the existence and stability of the five steady states of the model. Using Lyapunov functionals, we established the global stability of the steady states of the model. The theoretical results are confirmed by numerical simulations. [ABSTRACT FROM AUTHOR]

Malignant tumours are a major cause of mortality in humans. Currently used therapeutic regimens have not improved survival rates of patients suffering from malignant tumours much because of their limited efficacy and side-effects. A therapeutic approach that uses Newcastle disease virus ( NDV) represents an attractive new tool for tumour immunotherapy. The present review highlights the mechanisms and advances that are likely to have considerable impact on NDV virotherapy. Significant evidence exists regarding the oncolytic effects of NDV, suggesting its potential use in the treatment of various tumours. Furthermore, clinical trials have suggested that several NDV strains have the potential for cancer virotherapy with few side-effects compared with traditional treatments., Many studies have been performed to investigate the oncolytic mechanisms of NDV. Apoptosis following NDV infection may contribute to the observed oncolytic effects; however, NDV could also stimulate both innate and adaptive antitumour immune responses., For many years, different approaches have been investigated (or are in the process of being developed) regarding the use of NDV for the treatment of malignancies. Recent advances using reverse genetics have provided a means of generating recombinant NDV strains with improved oncolytic and immune regulatory properties. [ABSTRACT FROM AUTHOR]

It has become clear that the biological and clinical behaviour of malignant lymphoma is not only determined by the properties of the tumour cells themselves but are also largely by the interaction of the tumour cells with their nonmalignant microenvironment. The composition and functional status of the tumour microenvironment is highly variable between different classes of malignant lymphoma and may provide both growth-supportive and growth suppressive signals via components of the adaptive and innate immune response. In this review, the functional interactions and clinical consequences of these insights are discussed in indolent and aggressive B-cell lymphomas and in classical Hodgkin’s lymphoma. [ABSTRACT FROM AUTHOR]