Depletion of neutralising antibodies resensitises a secondary non-responder to botulinum A neurotoxin

The objective was to evaluate whether removal of neutralising antibodies potentially resensitises a secondary non-responder to botulinum neurotoxin A (BoNT/A). Neutralising antibodies directed against BoNT/A are produced during long term treatment with BoNT/A-hemagglutinin complex in up to 10% of patients with cervical dystonia. These patients become secondary non-responders. Other serotypes of BoNT are not yet generally available and may also bear the risk of inducing antibody formation. Plasma exchange (PE) (one treatment cycle) and immunoadsorption on a protein A column (IA-PA; three treatment cycles) was employed over 15 months to remove neutralising antibodies from a severely disabled secondary non-responder with cervical dystonia. After plasma exchange or IA-PA, BoNT/A was reinjected. Antibodies were measured with a sensitive functional toxin neutralising test. Repeated use of plasma exchange and IA-PA depleted neutralising antibodies to below the detection limit and subsequently allowed successful BoNT/A injection into dystonic muscles. No serious side effects were found related to the depletion of IgG. In conclusion PE or IA-PA performed before BoNT/A readministration may provide an alternative strategy in treating selected secondary non-responders who are severely disabled.     

The effect of low doses of nakom on the hormonal secretion of the hypothalamo-hypophyseal-adrenal system in patients with infantile cerebral palsy

The levels of hormones of hypothalamo-hypophyseal-adrenal system were measured in 14 10-14 year old children with infantile cerebral paralysis (ICP) with central catecholaminergic motor insufficiency. Contents of adrenocorticotropic hormone (ACTH), hydrocortisone (HC), somatotropic hormone, prolactin (P) were examined before and during Nacome administration (62.5 mg once daily in the morning). 110 patients of the same age with ICP and 18 children with acquired encephalopathy (EP) formed the control group. The elevations of ACTH, HC and P were revealed in spastic forms of ICP. Meanwhile nearly normal hormonal levels were observed in hyperkinetic forms of ICP and EP. The more pronounced effect was noted in "dopamine-dependent" children in which the drug's administration resulted in normalization of clinical and biochemical indices. Hyperkinetic phenomena revealed the connection between the character of neuromotor dyskinesias and the state of hypothalamo-hypophyseal-adrenal axis which is regulated by dopamine. The data obtained show hypofunction of dopaminergic neurotransmitter cerebral systems in patients with ICP that plays important pathogenetic role in development of disease with systemic manifestations.     

The rehabilitation of patients with a history of viral hepatitis using UHF therapy (460 MHz)

The results of the treatment of 316 patients with various injuries of abdomen are summarized. 144 (45.6%) of the patients were operated on vital indications (internal bleeding, peritonitis). Additional instrumental examination was necessary in 172 (54.4%) of the patients. Urgent diagnostic laparoscopy was performed in 118 of them. This procedure is indicated in patients with the absence of the symptoms of "acute abdomen" hospitalised in less than 2 hours from the moment of penetrating injury. It is also indicated in case of a doubtful diagnosis in a blunt injury of abdomen, and in alcoholic intoxication. Three groups of the patients were distinguished: 1) patients with indications for urgent surgery (38.1%); 2) patients with indications for conservative treatment (17.8%); 3) patients with indications for out-patient follow-up (44.1%). This policy made it possible to decrease the number of diagnostic laparotomies to 11%, the period of limited disability by 5.8 + 0.3 days, decrease lethality to 6%.     

Site-selected mutagenesis of a conserved nucleotide binding HXGH motif located in the ATP sulfurylase domain of human bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthase

3'-Phosphoadenosine-5'-phosphosulfate (PAPS) synthase is a bifunctional protein consisting of an NH2-terminal APS kinase and a COOH-terminal ATP sulfurylase. Both catalytic activities require ATP; the APS kinase domain involves cleavage of the beta-gamma phosphodiester bond of ATP, whereas the ATP sulfurylase domain involves cleavage of the alpha-beta phosphodiester bond of ATP. Previous mutational studies have suggested that beta-gamma phosphodiesterase activity involves a highly conserved NTP-binding P-loop motif located in the adenosine-5'-phosphosulfate kinase domain of PAPS synthases. Sequence alignment analysis of PAPS synthases and the superfamily of TagD-related nucleotidylyltransferases revealed the presence of a highly conserved HXGH motif in the ATP sulfurylase domain of PAPS synthases, a motif implicated in the alpha-beta phosphodiesterase activity of cytidylyltransferases. Thus, site-selected mutagenesis of the HXGH motif in the ATP sulfurylase domain of human PAPS synthase (amino acids 425-428) was performed to examine this possibility. Either H425A or H428A mutation produced an inactive enzyme. In contrast, a N426K mutation resulted in increased enzymatic activity. A G427A single mutant resulted in only a modest 30% reduction in catalytic activity, whereas a G427A/H428A double mutant produced an inactive enzyme. These results suggest an important role for the HXGH histidines in the ATP sulfurylase activity of bifunctional PAPS synthase and support the hypothesis that the highly conserved HXGH motif found in the ATP sulfurylase domain of PAPS synthases is involved in ATP binding and alpha-beta phosphodiesterase activity.     

Quantitative measures of job variety: an experimental study-based on a psychophysical scaling technique

This paper presents some quantitative measures of job variety based on entropy statistics of information theory and on a modification of the Turner-Lawrence measure. By means of the psychophysical scaling technique of magnitude estimation, subjective judgements of variety for a number of different job situations were obtained from a total of 42 subjects. Power models or linear models between perceived variety and its physical correlates were found to explain up to 99% of the variation in perceived variety. Since job variety is generally considered to have a significant influence on motivation and job satisfaction, such quantitative models may possess practical utility for job design and for systematic programmes of job enlargement or enrichment.     

The effect of task complexity on the human learning function

This experimental study analysed the effects of the complexity (entropy) of a repetitive tusk on the human looming function for the task. The results from 20 subjects revealed that the task entropy had a significant influence on the relationship between the performance (cycle time) and practice (the number of repetitions or cycle number). The model parameters for this relationship were found to be significantly and linearly related to the task entropy, the nominal rate of which varied within the maximum range of 0·9·to 6.1 bits/s     

Characterization of dihydrofolate reductase genes from trimethoprim-susceptible and trimethoprim-resistant strains of Enterococcus faecalis

PURPOSE: To understand the molecular mechanisms involved in protein-methylidene malonate 2.1.2 polymer interactions. METHODS: To assess the importance of electrostatic forces in polymer-protein interactions use was made of HSA and its derivatives, which were anionized by succinylation and aconitylation. Surface plasmon resonance measurements, using the three HSA molecules as immobilized ligands and polymer nanoparticles as analytes in the liquid phase, allowed the determination of initial kinetic constants and affinity constants at equilibrium at two different temperatures. RESULTS: Saturation of binding for the three proteins occurred at approximately 900 protein molecules/nanoparticle. The apparent affinity decreased with increasing electronegativity of the proteins. Surface plasmon resonance measurement of proteins, covalently linked to the chip matrix, showed a high affinity for the nanoparticles (K(A) approximately 10(10) M(-1) and confirmed the moderate decrease of affinity with increasing electronegativity of the modified albumins. Measurements at 25 and 37 degrees C showed no significant increase in the albumin-nanoparticle interactions. Dissociation of the proteins from the nanoparticles could only be realized with chaotropic salt solutions. CONCLUSIONS: These results suggest the molecular forces initiating the protein-nanoparticle interactions are mainly of electrostatic nature followed by stabilization by hydrophobic forces. The high affinity confirms the nanoparticles as excellent carriers for protein delivery.     

Predicting the morphological and hydraulic consequences of river rehabilitation

Decisions about reach‐scale river rehabilitation for the purposes of flood protection and ecological enhancement require prediction of the possible consequences of management alternatives. To provide such predictions, an integrative model is necessary that represents the cause–effect relations between rehabilitation options and morphological, hydraulic and ecological consequences. This paper describes the morphological and hydraulic submodel of such an integrative model. This submodel is further subdivided into four modules predicting: (1) channel morphology, (2) flooding (dike overtopping, floodplain flooding and bed moving floods), (3) velocity and depth distribution and (4) riverbed siltation. Model relationships come from results reported in the literature and new data analyses. By using quantities that are all either readily available or easily predictable for changed conditions, the model should be widely applicable, even for data‐limited situations. The overall model is implemented as a probability network to facilitate estimation of uncertainties in model results. An application of the model to a reach of the Thur River in Switzerland demonstrates its utility for predicting morphological and hydraulic consequences of a planned river widening. The full integrative model, including ecological endpoints, will be used together with quantitative assessments of stakeholder preferences to support rehabilitation decisions for a number of Swiss rivers. Copyright © 2007 John Wiley & Sons, Ltd.