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Hereditary Transthyretin Amyloidosis is a rare, progressive and life-threatening systemic disease with predominant peripheral and autonomic nervous system involvement caused by mutation of the transthyretin protein. The most common TTR mutation regarding to ATTRv is a substitution of a Methionine for a Valine at position 30 that predisposes TTR to form aggregates and fibrils. S100A8 protein levels were measured in plasma samples from ATTRV30M patients and healthy donors. Additionally, S100A8/9 levels were measured in Schwann cells after incubation with human WT or V30M TTR. Moreover, bone marrow derived macrophages of either genetic background were generated and the expression of S100A8/9 was measured in response to toll like receptors agonists. S100A8/A9 mRNA levels are decreased in HSF V30M mice as compared with the WT. Moreover, S100A8 protein levels were found downregulated in plasma samples from ATTRV30M patients. Furthermore, we provide evidence for a dysregulated S100 expression by Schwann cells in response to TTRV30M and by mutated macrophages in response to toll like receptors agonists. The presence of TTRV30M impacts S100 expression, possibly contributing to the impaired immune activation of Schwann cells in nerves from ATTRV30M patients. This may be linked to the diminished immune cellular infiltration in these nerves, contributing in this way for the neuronal dysfunction present in the disease. [ABSTRACT FROM AUTHOR]

Prior research described three stable patterns of organized behavior employed by infants to manage stressful interactive situations with their mothers in the Face-to-Face Still-Face paradigm (FFSF) at 3 and 9 months postpartum. The current longitudinal study expands this research by examining the extent to which these patterns predict infants' later attachment quality. For that purpose, 108 full-term infants and their mothers participated in the FFSF at 3 and 9 months, and in the Strange Situation at 12 months. Cross-tabulation analyses indicated a significant association between (1) the Social-positive oriented pattern and secure attachment, (2) the Distressed-inconsolable pattern and insecure-ambivalent attachment, and (3) the Self-comfort oriented pattern and insecure-avoidant attachment. Our results contribute to a growing body of studies suggesting that patterns of infants' regulatory behavior assessed during the FFSF during the first year, may be early developmental precursors of attachment patterns at 12 months. [ABSTRACT FROM AUTHOR]

An overview of our experiences in the field of immunoliposomal anticancer drugs is provided with respect to choice of ligand, and choice of model system, in order to provide some guidance as to the rational use of this new technology. Liposomes targeted by either peptide or monoclonal antibodies showed significantly higher binding to their respective target cells in vitro compared to non-targeted liposomes in all model systems examined. This higher binding led to higher cytotoxicities relative to nontargeted liposomes. For the immunoliposomes to deliver their entrapped drug to target cell in vivo, long circulations half-lives are required. We have evaluated the pharmacokinetics of liposomes prepared by several different coupling techniques, and have found significant differences in the clearance of these immunoliposomes from the circulation. Immunoliposomes prepared with whole anti-CD19 IgG coupled by the Mal-PEGDSPE method demonstrated a short plasma half-life, which may reflect the random orientation of the MAb on the liposome surface. Coupling methods that mask or eliminate the Fc region result in immunoliposomes that have clearance rates more similar to untargeted liposomes. Insertion of peptides or antibodies into pre-formed liposomes through incubation with ligand-coupled PEG micelles resulted in immunoliposomes, termed post-insertion liposomes, that demonstrated comparable in vitro binding, pharmacokinetic profiles and in vivo therapeutic efficacy to liposomes made by conventional coupling methods. The therapeutic efficacy of liposomes, prepared by various coupling methods and targeted by different ligands, was compared in several different animal models of either haematological malignancies, pseudometastatic disease or solid tumours. In our hands, successful in vivo targeting has been obtained when the target is either small or readily accessible from the vasculature, where the liposomes have longer circulating half-lives and/or where a ligand against... [ABSTRACT FROM AUTHOR]

Highlights from the article: Inflammation is a hallmark of several neurodegenerative disorders including familial amyloid polyneuropathy (FAP). Our recent data highlight the potential of CtsE as a novel FAP biomarker and a possible modulator for innate immune cell chemotaxis in the PNS of FAP patients [[3]].

AbstractBackgroundMethodsResultsConclusionsHereditary transthyretin amyloidosis (ATTRv amyloidosis) is an inherited disease, where the study of family history holds importance. This study evaluates the changes of age-of-onset (AOO) and other age-related clinical factors within and among families affected by ATTRv amyloidosis.We analysed information from 934 trees, focusing on family, parents, probands and siblings relationships. We focused on 1494 female and 1712 male symptomatic ATTRV30M patients. Results are presented alongside a comparison of current with historical records. Clinical and genealogical indicators identify major changes.Overall, analysis of familial data shows the existence of families with both early and late patients (1/6). It identifies long familial follow-up times since patient families tend to be diagnosed over several years. Finally, results show a large difference between parent-child and proband-patient relationships (20–30 years).This study reveals that there has been a shift in patient profile, with a recent increase in male elderly cases, especially regarding probands. It shows that symptomatic patients exhibit less variability towards siblings, when compared to other family members, namely the transmitting ancestors’ age of onset. This can influence genetic counselling guidelines. [ABSTRACT FROM AUTHOR]