Selective Genetics (United States)

This research assessed the feasibility of Social Communication Anxiety Treatment (S-CAT) developed by Elisa Shipon-Blum, a brief multimodal approach, to increase social communication in 40 children aged 5-12 years with selective mutism (SM). SM is a disorder in which children consistently fail to speak in specific situations although they have the ability to do so. Key features of this approach are the SM-Social Communication Comfort Scale (SCCS), transfer of control (ToC), a nonchalant therapeutic style, and cognitive-behavioral strategies over a brief time frame. Following 9 weeks of treatment, children showed significant gains in speaking frequency on all 17 items from the Selective Mutism Questionnaire (SMQ), a standardized measure of SM severity. Children also showed decreased levels of anxiety and withdrawal as reported by parents on the Child Behavior Checklist (CBCL). SM initial symptom severity and family therapy compliance, but not duration of SM, contributed to treatment outcomes.

Efficient neuronal gene therapy is a goal for the long-term repair and regeneration of the injured central nervous system (CNS). We investigated whether targeting cDNA to neurons with cholera toxin b chain conjugated non-viral polyplexes led to increased efficiency of non-viral gene transfer in the CNS. Here, we illustrate the potential for this strategy by demonstrating enhanced transfection of a differentiated neuronal cell type, PC12. In vitro transfection efficiency of a cholera toxin b chain-poly(D-lysine) molecular conjugate (CTb-K(100)) was compared by fluorescence-activated cell sorting (FACS) analysis of green fluorescent protein (GFP) expression and luminometric measurement of beta-galactosidase (beta-gal) expression, to untargeted poly(D-lysine) (K(100)) in undifferentiated and NGF-differentiated PC12 cells. Transfection of undifferentiated PC12 cells with CTb-K(100) polyplexes resulted in a 36-fold increase in levels of pCMV-DNA(LacZ) expression and a 20-fold increase in the frequency of transduction with pCMV-DNA(GFP), compared with untargeted K(100) polyplexes. Treatment of PC12 cells with 50 ng/ml/day of NGF for 14 days led to differentiation to a neuronal phenotype. Transfection of NGF-differentiated cells with CTb-K(100) polyplexes resulted in a 133-fold increase in levels of pCMV-DNA(LacZ) expression and a 11-fold increase in the percentage of cells transduced with pCMV-DNA(GFP), compared with untargeted K(100) polyplexes. Transfection was dependent on CTb, with CTb-K(100)-mediated transfections competitively inhibited with free CTb in both PC12 phenotypes. Non-viral systems for gene transfer in damaged CNS show superior toxicological profiles to most viruses but are limited by inefficient and non-selective gene expression in target tissue. Cholera toxin is known to interact preferentially with neuronal cells of the central and peripheral nervous systems, mediating binding through the b subunit, CTb, and the pentasaccharide moiety of the gangliosaccharide, GM1, which is present at high levels on the neuronal cell surface. Here, we show that a molecular conjugate of the CTb subunit, covalently linked to poly(D-lysine), is able to successfully target and significantly enhance transfection of a neuronal cell type, NGF-differentiated rat PC12 pheochromocytoma cells. This observation encourages the further development of non-viral strategies for the delivery of therapeutic genes to neurons.

Interest in the possibility of successful interventions for personality disorders has increased during the past 2 years, mainly because of heightened awareness of the diagnosis. In particular, efficacy of treatments for borderline personality disorder has improved, with good evidence for the superiority of focused day hospital psychotherapy compared with standard care, and somewhat less convincing evidence for the value of sodium valproate in this condition. Other reports also suggest that both psychosocial and pharmacological treatments are both likely to have a significant role to play in the treatment of all personality disorders, and for the first time these modalities are being properly evaluated in good research studies. The view that personality disorders are untreatable can now be challenged with serious evidence.

Memory processing in humans is essential for consciousness, cognitive-behavioral development and individual biography. In epilepsy, declarative memory functions show characteristic patterns of impairment when mesiotemporal and associated neocortical structures are affected by lesions, ongoing epileptic activity, or the undesired effects of conservative or operative treatment. Major issues are thus the etiology, onset and course of memory impairment, as well as the prevention of further memory decline during treatment. New input in the field has resulted from improved imaging techniques, sophisticated experimental study designs, more selective surgical approaches, and new antiepileptic drugs.

Body dysmorphic disorder, a distressing and impairing preoccupation with an imagined or slight defect in appearance, is an intriguing and under-recognized disorder that has only recently been systematically studied. Recent research findings indicate that body dysmorphic disorder is relatively common, causes notable distress and impairment in functioning, and is associated with markedly poor quality of life. Available data on treatment response, while still limited, suggest that serotonin-reuptake inhibitors and cognitive-behavioral therapy are often effective for body dysmorphic disorder. Further research is needed on all aspects of this understudied and severe mental disorder.

Psychiatric illness in people with mental retardation has attracted increasing clinical and research interest over the past year. In recognition of this trend, the Journal of Intellectual Disability Research recently published special issues on mental health and intellectual disability. A number of books have also been published on this theme in recent years. Despite the improvement in quality of research, funding for work in this important clinical area remains inadequate.

The 1990s have seen a resurgence of interest in psychopharmacology. This has coincided with new medicines marketed for the treatment of neurological or mental health problems. There are new medicines for the treatment of depression, schizophrenia, Alzheimer's disease and epilepsy, all of which could have value for people with mental retardation.

This brief review points to work that largely concerns the detection of the common mental disorders of depression and anxiety amongst older patients in primary care. There is now evidence for effective screening questionnaires to help general practitioners in their work.

Basic fibroblast growth factor (FGF2) has potent mitogenic and angiogenic activities that have been implicated in tumor development and malignant progression. The biological effects of FGF2 and other members of the FGF ligand family are mediated by 4 transmembrane tyrosine kinase receptors (FGFRs). To better understand the roles of FGFRs in cancer, the expression of FGF2 and each of the 4 FGFRs was assessed by RNase protection analysis of 60 human tumor cell lines, representing 9 tumor types. Expression of at least one FGFR isoform was detected in 90% and FGF2 mRNA in 35% of the cell lines. Our comprehensive analysis of FGF2 and FGFR expression in human tumor cell lines provides evidence that FGF signaling pathways are active in a majority of human tumor cell lines, and lends support to the development of anti-tumor strategies that target FGFRs. Int. J. Cancer 81:451–458, 1999. © 1999 Wiley-Liss, Inc.