Melchor Álvarez de Mon

Molecular analysis of HIV-1 gp120 antibody response using isotype IgM and IgG phage display libraries from a long-term non-progressor HIV-1- infected individual

To characterize the variable heavy chain (VH)3 antibody response to HIV‐1 gp120, we analyzed a panel of IgM and IgG1 Fab fragments from phage display isotype libraries from a long‐term, non‐progressor HIV‐1‐infected individual. The IgM Fab antibodies isolated had low affinity for gp120, were not restricted to a particular VH3 germ‐line gene, and consisted mainly of unmutated VH genes. In contrast, IgG Fab fragments were gp120 specific, with high affinity and extensive somatic mutation; all were clonally related and were derived from a single VH3 germ‐line gene (DP50). One IgG Fab (S8) has DP50 VH region nucleotide substitutions identical to those of IgM Fab M025 and uses similar DH and JH segments, suggesting that S8 arose from M025 by isotype switching. In addition, somatic mutation in the IgG heavy chain third complementarity‐determining region results in a 100‐fold affinity increase for gp120, which correlates with a similar increase in neutralization capacity. These results imply that in vivo IgM to IgG isotype switch and affinity maturation may be important for protection and long‐term survival in certain HIV‐1‐infected individuals.

Interferon-alpha-2b enhances the natural killer activity of patients with transitional cell carcinoma of the bladder

Background. Transitional cell carcinoma (TCC) of the bladder is associated with alterations in the immune system of the host. The authors demonstrated that in patients with bladder carcinoma there is a negative correlation between the levels of natural killer (NK) activity and the clinical evolution and pathologic stages of disease.

Mindfulness, Resilience, and Burnout Subtypes in Primary Care Physicians: The Possible Mediating Role of Positive and Negative Affect

Purpose: Primary care health professionals suffer from high levels of burnout. The aim of the present study was to evaluate the associations of mindfulness and resilience with the features of the burnout types (overload, lack of development, neglect) in primary care physicians, taking into account the potential mediating role of negative and positive affect. Methods: A cross-sectional design was used. Six hundred and twenty-two Spanish primary care physicians were recruited from an online survey. The Mindful Attention Awareness Scale (MAAS), Connor-Davidson Resilience Scale (CD-RISC), Positive and Negative Affect Schedule (PANAS), and Burnout Clinical Subtype Questionnaire (BCSQ-12) questionnaires were administered. Polychoric correlation matrices were calculated. The unweighted least squares (ULS) method was used for developing structural equation modeling. Results: Mindfulness and resilience presented moderately high associations (φ = 0.46). Links were found between mindfulness and overload (γ = −0.25); resilience and neglect (γ = −0.44); mindfulness and resilience, and negative affect (γ = −0.30 and γ = −0.35, respectively); resilience and positive affect (γ = 0.70); negative affect and overload (β = 0.36); positive affect and lack of development (β = −0.16). The links between the burnout types reached high and positive values between overload and lack of development (β = 0.64), and lack of development and neglect (β = 0.52). The model was a very good fit to the data (GFI = 0.96; AGFI = 0.96; RMSR = 0.06; NFI = 0.95; RFI = 0.95; PRATIO = 0.96). Conclusions: Interventions addressing both mindfulness and resilience can influence burnout subtypes, but their impact may occur in different ways, potentially mediated by positive and negative affect. Both sorts of trainings could constitute possible tools against burnout; however, while mindfulness seems a suitable intervention for preventing its initial stages, resilience may be more effective for treating its advanced stages.

Differential Oxidative Stress Induced by Dengue Virus in Monocytes from Human Neonates, Adult and Elderly Individuals

Changes in immune response during lifespan of man are well known. These changes involve decreased neonatal and elderly immune response. In addition, it has been shown a relationship between immune and oxidative mechanisms, suggesting that altered immune response could be associated to altered oxidative response. Increased expression of nitric oxide (NO) has been documented in dengue and in monocyte cultures infected with different types of dengue virus. However, there is no information about the age-dependent NO oxidative response in humans infected by dengue virus. In this study, monocyte cultures from neonatal, elderly and adult individuals (n = 10 each group) were infected with different dengue virus types (DENV- 1 to 4) and oxidative/antioxidative responses and apoptosis were measured at days 1 and 3 of culture. Increased production of NO, lipid peroxidation and enzymatic and nonenzymatic anti-oxidative responses in dengue infected monocyte cultures were observed. However, neonatal and elderly monocytes had lower values of studied parameters when compared to those in adult-derived cultures. Apoptosis was present in infected monocytes with higher values at day 3 of culture. This reduced oxidant/antioxidant response of neonatal and elderly monocytes could be relevant in the pathogenesis of dengue disease.

Increased cytokine/chemokines in serum from asthmatic and non-asthmatic patients with viral respiratory infection.

Respiratory viral infections can induce different cytokine/chemokine profiles in lung tissues and have a significant influence on patients with asthma. There is little information about the systemic cytokine status in viral respiratory‐infected asthmatic patients compared with non‐asthmatic patients.

The Role of IFN-β during the Course of Sepsis Progression and Its Therapeutic Potential

Sepsis is a complex biphasic syndrome characterized by both pro- and anti-inflammatory immune states. Whereas early sepsis mortality is caused by an acute, deleterious pro-inflammatory response, the second sepsis phase is governed by acute immunosuppression, which predisposes patients to long-term risk for life-threatening secondary infections. Despite extensive basic research and clinical trials, there is to date no specific therapy for sepsis, and mortality rates are on the rise. Although IFN-β is one of the most-studied cytokines, its diverse effects are not fully understood. Depending on the disease or type of infection, it can have beneficial or detrimental effects. As IFN-β has been used successfully to treat diverse diseases, emphasis has been placed on understanding the role of IFN-β in sepsis. Analyses of mouse models of septic shock attribute a pro-inflammatory role to IFN-β in sepsis development. As anti-inflammatory treatments in humans with antibodies to TNF-α or IL1-β resulted disappointing, cytokine modulation approaches were discouraged and neutralization of IFN-β has not been pursued for sepsis treatment. In the case of patients with delayed sepsis and immunosuppression, there is a debate as to whether the use of specific cytokines would restore the deactivated immune response. Recent reports show an association of low IFN-β levels with the hyporesponsive state of monocytes from sepsis patients and after endotoxin tolerance induction. These data, discussed here, project a role for IFN-β in restoring monocyte function and reversing immunosuppression, and suggest IFN-β-based additive immunomodulatory therapy. The dichotomy in putative therapeutic approaches, involving reduction or an increase in IFN-β levels, mirrors the contrasting nature of the early hyperinflammatory state and the delayed immunosuppression phase.