The transferrin binding protein B of Moraxella catarrhalis elicits bactericidal antibodies and is a potential vaccine antigen

The transferrin binding protein genes (tbpA and tbpB) from two strains of Moraxella catarrhalis have been cloned and sequenced. The genomic organization of the M. catarrhalis transferrin binding protein genes is unique among known bacteria in that tbpA precedes tbpB and there is a third gene located between them. The deduced sequences of the M. catarrhalis TbpA proteins from two strains were 98% identical, while those of the TbpB proteins from the same strains were 63% identical and 70% similar. The third gene, tentatively called orf3, encodes a protein of approximately 58 kDa that is 98% identical between the two strains. The tbpB genes from four additional strains of M. catarrhalis were cloned and sequenced, and two potential families of TbpB proteins were identified based on sequence similarities. Recombinant TbpA (rTbpA), rTbpB, and rORF3 proteins were expressed in Escherichia coli and purified. rTbpB was shown to retain its ability to bind human transferrin after transfer to a membrane, but neither rTbpA nor rORF3 did. Monospecific anti-rTbpA and anti-rTbpB antibodies were generated and used for immunoblot analysis, which demonstrated that epitopes of M. catarrhalis TbpA and TbpB were antigenically conserved and that there was constitutive expression of the tbp genes. In the absence of an appropriate animal model, anti-rTbpA and anti-rTbpB antibodies were tested for their bactericidal activities. The anti-rTbpA antiserum was not bactericidal, but anti-rTbpB antisera were found to kill heterologous strains within the same family. Thus, if bactericidal ability is clinically relevant, a vaccine comprising multiple rTbpB antigens may protect against M. catarrhalis disease.     

Laminin and alpha-dystroglycan mediate acetylcholine receptor aggregation via a MuSK-independent pathway

Specific isoforms of laminin (LN) are concentrated at neuromuscular junctions (NMJs) where they may participate in synaptic organization or function. In myotubes from C2 cells, LN is concentrated within the majority of spontaneous acetylcholine receptor (AChR) aggregates. Neural agrin substantially increases this colocalization, suggesting that agrin can recruit LN into AChR aggregates. Addition of LN to C2 myotubes induces a more than twofold increase in the number of AChR aggregates. These aggregates have a larger size and are more dense than are those induced by agrin, suggesting that LN is involved in the growth and/or stabilization of AChR aggregates. Consistent with this hypothesis, an antiserum to LN reduces the size of individual AChR aggregates but increases their number. In C2 myotubes, extracellular matrix receptors containing the integrin beta1 subunit are poorly colocalized with AChR aggregates, suggesting that integrins may not be involved in LN-induced aggregation. In contrast, almost all AChR aggregates are associated with dystroglycan immunoreactivity, and monoclonal antibody (mAb) IIH6 against alpha-dystroglycan (alpha-DG), a LN and agrin receptor, causes a concentration-dependent inhibition of LN-induced aggregation. Moreover, S27 cells, which lack a functional alpha-DG, and two C2-derived cell lines expressing antisense DG mRNA fail to aggregate AChRs in response to LN. Finally, LN-induced AChR aggregation does not involve the phosphorylation of the muscle-specific tyrosine kinase receptor (MuSK) or the AChR beta subunit. We hypothesize that the interaction of LN with alpha-DG contributes to the growth and/or stabilization of AChR microaggregates into macroaggregates at the developing NMJ via a MuSK-independent mechanism.     

Early effective suppression of inflammation in rheumatoid arthritis reduces radiographic progression

OBJECTIVE: To evaluate the effect of early 'aggressive' drug treatment on radiographic progression in patients with recent-onset rheumatoid arthritis (RA), compared to conventional stepwise increasing intensity of treatment. DESIGN: Prospective follow-up study with an experimental group and a historical control group both divided into a high-risk subgroup and a low-risk subgroup, based on prognostic factors. The effect of the 'aggressive' and the conventional treatment strategy was compared between both high-risk groups; the low-risk groups, both treated according to the conventional treatment strategy, were used to ensure internal consistency between the experimental and the historical groups. PATIENTS: A total of 228 consecutive patients with recent-onset RA (complaints < 1 yr at study entry). METHODS: The 'aggressive' drug treatment consisted of institution of relatively fast-acting disease-modifying anti-rheumatic drugs (DMARDs) (sulphasalazine, methotrexate) immediately after diagnosis, and rapid adjustment of dosage and/or drug in the case of insufficient response as measured by a change in C-reactive protein (CRP) level. Radiographic damage was assessed according to a modified version of Sharp's method and cumulative disease activity expressed as CRP-area under the curve (CRP-AUC). The occurrence of side-effects was also evaluated. RESULTS: After 2 yr of follow-up, comparison of the two high-risk subgroups showed the radiographic progression in the 'aggressively' treated subgroup to be significantly lower than that in the control group [Sharp score: median (range) 26 (0-100) vs 35 (1-188); P = 0.03]. Cumulative CRP values were also significantly lower than in the control high-risk subgroup [CRP-AUC: median (range) 1963 (212-8515) vs 3025 (46-15 632) mg.week/1; P = 0.002). This was achieved without an increase in the occurrence of side-effects. There was no difference between the two low-risk subgroups with regard to entry characteristics, CRP-AUC values or radiological progression, indicating comparability between the two groups. CONCLUSION: Early 'aggressive' drug treatment, using sulphasalazine and/or methotrexate, aimed at reduction of the CRP level, significantly reduces the (rate of) radiographic progression in RA.     

A mathematical approximation for the solution of a static indentation test

The aim of this study was to compare the incidence of acute adverse events and long-term outcome of two different surfactant dosing procedures in respiratory distress syndrome (RDS). The effects of two surfactant dosing procedures on the incidence of transient hypoxia and bradycardia, gas exchange, ventilatory requirements and 28 d outcome were compared. The patients, comprising 102 infants (birthweight 600-2000 g) with RDS on mechanical ventilation with FiO2 > or = 0.4, were randomized at 2-24 h to receive 200 mg kg(-1) of Curosurf; in 56 it was given by bolus delivery, and in 55 by a simplified technique (dose given in 1 min via a catheter introduced through a side-hole in the tracheal tube adaptor. The baby's position was not changed and ventilation was not interrupted). Two additional surfactant doses (100 mg kg(-1)) were also given, by the same method, if ventilation with FiO2 > or = 0.3 was needed 12 and 24 h after the initial dose. The number of episodes of hypoxia and/or bradycardia was similar in both groups. A slight and transient increase in PaCO2 was observed in the side-hole group. The efficacy of the surfactant, based on oxygenation improvement, ventilator requirements, number of doses required and incidence of air leaks, was similar. No differences were observed in the incidence of intraventricular haemorrhage, patent ductus arteriosus, bronchopulmonary dysplasia or survival. In conclusion, a simplified surfactant dosing procedure not requiring fractional doses, ventilator disconnection, changes in the baby's position or manual bagging was found to be as effective as bolus delivery. The number of dosing-related transient episodes of hypoxia and bradycardia was not decreased by the slow, 1 min, side-hole instillation procedure.     

Analysis of nickel refinery dusts

After characterization of bulk samples by inductively coupled plasma emission spectroscopic (ICP-ES) quantitative analysis and X-ray powder diffraction studies, single particle techniques using quantitative image analysis, scanning electron microscopy--energy dispersive analysis by X-ray, and finally laser beam ionization mass spectrometry analysis (LIMA) for surface analysis have been applied to historical nickel refinery dust samples from the nickel refining plant at Clydach in Wales. There were two historical samples of processed material from 1920 and 1929. These samples had a remarkably small particle size range, mean 3 microns and range, 0.75-24 microns. The most significant difference in elemental composition was the presence of 10% arsenic in the 1920 sample compared with 1% in the 1929 sample. The X-ray spectra revealed the presence of NiO in both. However, surprisingly, CuO was identified only in the 1929 sample. Of particular interest was the presence of a component, in the 1920 sample only, identified as the mineral orcelite, a copper-iron-nickel-arsenide-sulphide mineral, predominantly, Ni5-XAs2. Using the LIMA technique, it was found that in both samples, arsenic and arsenic derivative peaks are prominent, indicating the surface availability of arsenic compounds.     

Nitric oxide influences the release of histamine and glutamate in the rat hypothalamus

This study applied a social-genetic perspective to examine hypotheses concerning displays of cooperation. The sample included children from 14 monozygotic and 16 dizygotic twin pairs, organized into 30 unfamiliar partnerships. Two puzzle completion sessions were videotaped and evaluated on five dimensions of cooperation. Repeated measures of analysis of variance indicated significantly higher ratings among female than male pairs on Overall Cooperation, Mutuality of Goal and Accommodation. Contrary to expectation, social-interactional differences between unfamiliar MZ and DZ dyads were not detected. Findings are discussed with reference to new research perspectives on cooperative behavior.