Neuroleptic-induced movement disorders in a naturalistic schizophrenia population: diagnostic value of actometric movement patterns

<p>Abstract</p> <p>Background</p> <p>Neuroleptic-induced movement disorders (NIMDs) have overlapping co-morbidity. Earlier studies have described typical clinical movement patterns for individual NIMDs. This study aimed to identify specific movement patterns for each individual NIMD using actometry.</p> <p>Methods</p> <p>A naturalistic population of 99 schizophrenia inpatients using conventional antipsychotics and clozapine was evaluated. Subjects with NIMDs were categorized using the criteria for NIMD found in the Diagnostic and Statistical Manual for Mental Disorders – Fourth Edition (DSM-IV).</p> <p>Two blinded raters evaluated the actometric-controlled rest activity data for activity periods, rhythmical activity, frequencies, and highest acceleration peaks. A simple subjective question was formulated to test patient-based evaluation of NIMD.</p> <p>Results</p> <p>The patterns of neuroleptic-induced akathisia (NIA) and pseudoakathisia (PsA) were identifiable in actometry with excellent inter-rater reliability. The answers to the subjective question about troubles with movements distinguished NIA patients from other patients rather well. Also actometry had rather good screening performances in distinguishing akathisia from other NIMD. Actometry was not able to reliably detect patterns of neuroleptic-induced parkinsonism and tardive dyskinesia.</p> <p>Conclusion</p> <p>The present study showed that pooled NIA and PsA patients had a different pattern in lower limb descriptive actometry than other patients in a non-selected sample. Careful questioning of patients is a useful method of diagnosing NIA in a clinical setting.</p

Suppression of p75 Neurotrophin Receptor Surface Expression with Intrabodies Influences Bcl-xL mRNA Expression and Neurite Outgrowth in PC12 Cells

Background: Although p75 neurotrophin receptor (p75NTR) is the first neurotrophin receptor isolated, its diverse physiological functions and signaling have remained elusive for many years. Loss-of-function phenotypic analyses for p75NTR were mainly focused at the genetic level; however these approaches were impacted by off-target effect, insufficient stability, unspecific stress response or alternative active splicing products. In this study, p75NTR surface expression was suppressed for the first time at the protein level by endoplasmic reticulum (ER) retained intrabodies. Results: Three monoclonal recombinant antibody fragments (scFv) with affinities in the low nanomolar range to murine p75NTR were isolated by antibody phage display. To suppress p75NTR cell surface expression, the encoding genes of these scFvs extended by the ER retention peptide KDEL were transiently transfected into the neuron-like rat pheochromocytoma cell line PC12 and the mouse neuroblastoma x mouse spinal cord hybrid cell line NSC19. The ER retained intrabody construct, SH325-G7-KDEL, mediated a downregulation of p75NTR cell surface expression as shown by flow cytometry. This effect was maintained over a period of at least eight days without activating an unfolded protein response (UPR). Moreover, the ER retention of p75NTR resulted in downregulation of mRNA levels of the anti-apoptotic protein Bcl-xL as well as in strong inhibition of NGF-induced neurite outgrowth in PC12 cells. Conclusion: The ER retained intrabody SH325-G7-KDEL not only induces phenotypic knockdown of this p75NTR but als

Isolation and Characterisation of a Human-Like Antibody Fragment (scFv) That Inactivates VEEV In Vitro and In Vivo

Venezuelan equine encephalitis virus (VEEV) belongs to the Alphavirus genus and several species of this family are pathogenic to humans. The viruses are classified as potential agents of biological warfare and terrorism and sensitive detection as well as effective prophylaxis and antiviral therapies are required

The distribution of EM waves scattering from cutaneous surface

The general explicit discretized solution for the Beckmann mathematical 2-D model, for the scattering of electromagnetic waves, from a rough boundary (a cutaneous surface was selected for application) was determined numerically and found in accordance with the reality of its topographical quantitative parameters, obtained by a 3-D automated wide range profilometer

A NEW MUTATION IN THE HEXA GENE ASSOCIATED WITH A SPINAL MUSCULAR-ATROPHY PHENOTYPE

We describe two adult siblings who had had mild GM(2) gangliosidosis since childhood. They presented with spinal muscular atrophy and dysarthria, and one sibling also had mental disturbances. Laboratory studies established the diagnosis of the B1 variant of GM(2) gangliosidosis, because the hexosaminidase (Hex) A deficiency was not present upon testing with the unsulfated synthetic substrate 4-methylumbelliferyl N-acetylglucosaminide. HEXA gene analysis proved that the patients are compound heterozygotes for the previously identified G(533)-->A mutation and for a new mutation, G(1171)-->A, at exon 11. This new mutation affects a conserved amino acid and results in a Val-->Met substitution at position 391 of the HEXA gene, Full sequence of the alpha-subunit cDNA of Hex A revealed no other mutation. Assays for Hex A activities in patients suspected of having GM(2) gangliosidosis should be performed with the sulfated substrate 4-methylumbelliferyl N-acetylglucosamine 6-sulfate