ABSTRACT
OBJECTIVE: This article outlines an approach to assessing the quality of relationships between young foster children and their carers. These children are at high risk of disorganised attachment relationships and of developmental psychopathology given their relational experiences prior to and in care. During a semi-structured play interaction the emphasis is on identifying behaviours of clinical interest. This can be complex given the likelihood of atypical or unexpected behaviours expressed within relationships. METHOD: The paper draws on literature on the clinical application of attachment theory to the assessment of relationships and on the authors' experience of developing and delivering an assessment and intervention service for children aged 0 to 5-years-old within a mental health service for children in foster care. Clinical material is used to illustrate and develop the issues. CONCLUSION: The case for including a semi-structured observational procedure as part of a comprehensive assessment of foster children and their carers is outlined. This is argued to have more clinical utility than formal approaches to attachment classification. The benefits of including a semi-structured and relational approach to clinical assessment of foster children are outlined along with the need to be cautious in the use of attachment related terminology when formal assessments have not been undertaken.
Subject(s)
Caregivers/psychology , Foster Home Care/psychology , Interpersonal Relations , Object Attachment , Parent-Child Relations , Adult , Child, Preschool , Humans , InfantABSTRACT
Antibody-based therapeutics play a vital role in the treatment of certain cancers; however, despite commercial success, various strategies are being pursued to increase their potency and hence improve patient outcomes. The use of antibodies to deliver a cytotoxic payload offers a promising alternative for more efficacious therapies. Immunotoxins are composed of an internalizing antibody fragment linked to a bacterial or plant toxin. Once internalized, the payload, such as Pseudomonas exotoxin A (PE), blocks protein synthesis and induces apoptosis. Typically, immunotoxins are developed by first isolating a tumor-specific antibody, which is then either chemically linked to a toxin or reengineered as a fusion protein. Here, the authors describe the development of Fusogenics, an immunotoxin-based screening method that selects internalizing tumor-specific antibodies using a functional assay. Selected immune library clones were characterized and shown to be selective against normal tissues and specific to tumor tissues. In summary, the Fusogenics immunotoxin platform represents a unique, single-step selection approach combining specificity and functionality to isolate novel internalizing tumor-specific antibody fragments with potential for direct clinical application in the treatment of cancer.
Subject(s)
Drug Screening Assays, Antitumor/methods , Immunotoxins , ADP Ribose Transferases/genetics , ADP Ribose Transferases/isolation & purification , Antibodies, Neoplasm/biosynthesis , Antibodies, Neoplasm/isolation & purification , Apoptosis , Bacterial Toxins/genetics , Bacterial Toxins/isolation & purification , Cell Line, Tumor , Escherichia coli , Exotoxins/genetics , Exotoxins/isolation & purification , Gene Library , High-Throughput Screening Assays , Humans , Immunoglobulin Fragments/biosynthesis , Immunoglobulin Fragments/genetics , Immunoglobulin Fragments/isolation & purification , Immunotoxins/genetics , Immunotoxins/immunology , Immunotoxins/isolation & purification , Neoplasms/immunology , Neoplasms/therapy , Organ Specificity , Recombinant Fusion Proteins/biosynthesis , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/isolation & purification , Virulence Factors/genetics , Virulence Factors/isolation & purification , Pseudomonas aeruginosa Exotoxin AABSTRACT
We have investigated infection and pathogenesis of Autographa californica multiple nucleopolyhedrovirus (AcMNPV) in Anticarsia gemmatalis (velvetbean caterpillar) larvae using a lacZ recombinant virus (AcMNPV-hsp70/lacZ) to track the temporal progression of infection in the midgut intestine and haemocoel. A. gemmatalis was highly resistant to fatal infection by occlusion bodies (OBs; LD(50)>5.5 x 10(5) OB) and budded virus (BV; LD(50)>3 x 10(5) BV) administered via oral and systemic routes, respectively. Orally administered occlusion-derived virus (ODV) efficiently attached and fused to midgut cells; however, high levels of infection-induced apoptosis limited infection in the midgut. Transcriptional analysis of AcMNPV genes expressed in the midgut of OB-inoculated A. gemmatalis larvae showed high levels of mRNA encoding the major capsid protein VP39 in the absence of immediate-early transactivator 1 (ie-1) expression. In the midgut, virus was efficiently transferred from infected midgut epithelial cells to nearby tracheolar cells and circulating haemocytes to initiate systemic infection in the haemocoel. However, haemocoelic BV did not efficiently disseminate infection and only cuticular epidermal cells displayed high levels of viral infection. Flow cytometry analysis of haemocytes isolated from BV-inoculated A. gemmatalis larvae showed low-level expression of the BV envelope protein GP64 on the cell surface, suggesting that A. gemmatalis haemocytes have a limited capacity for amplifying virus. These results show that AcMNPV is not an effective biological control agent for limiting crop damage caused by A. gemmatalis larvae.
