Triple check for antigen specificity of B cells during germinal centre reactions

Somatic hypermutation of the immunoglobulin variable genes during germinal reactions might permit the expansion of B-cell clones with unwanted (e.g. autoreactive) specificity. Here, Ernst Lindhout and colleagues propose three antigen-specific checkpoints that ensure the appropriate antigen specificity of activated B cells is maintained by regulating the activation, selection and further differentiation of B cells.     

Evaluation of hydroxylapatite/poly(l-lactide) composites: physico-chemical properties

The aim of this in vitro study was to examine the physico-chemical behaviour of hydroxylapatite/poly(l-lactide) (HA/PLLA) composites in solution tests. The polymer PLLA, the composites 30 wt% HA/PLLA (C30) and 50 wt% HA/PLLA (C50) and a one-side HA-coated PLLA (HAcP) were evaluated. Rectangular specimens were incubated in various acellular aqueous buffer solutions [citrate, Gomori's and phosphate-buffered saline (PBS)] up to 24 weeks. Data for cumulative release of calcium, phosphate and l-lactate release in solutions containing C30 or C50 showed linear patterns. Release data for solutions containing HAcP combined with scanning micrographs, X-ray microanalysis and X-ray diffraction patterns of the specimens in time showed that the plasma-sprayed HA coating on PLLA dissolves significantly, progressively in the first weeks and almost completely within the tested period of 24 weeks in vitro. A precipitate of scaly crystallites (calcium phosphates) was observed at the HA coating-PBS interface. After 24 weeks incubation all materials were still above their initial weight, indicating that swelling still exceeded dissolution. Application of C30, C50 and HAcP as implant materials seems interesting where initial stabilization through bone bonding is needed or where the linear release of constituents is a requirement. HAcP has the advantage that the HA coating acts as a hydrolysis barrier and consequently delays the degradation of PLLA in vitro.     

Diagnosis of systemic causes of uveitis; a matter of ophthalmologist and internist

OBJECTIVE: To assess how often the aetiology is established in patients with uveitis, what systemic disease are found and what is the contribution of the internist to the diagnostic process. DESIGN: Retrospective study. SETTING: University Hospital Leiden, the Netherlands. METHOD: From January 1987 to April 1992, 342 patients presented with uveitis. All patients underwent a standard ophthalmological examination. Referral to an internist and individualised laboratory screening followed in patients with recurrent, chronic, bilateral or panuveitis. Recorded were: ophthalmological data, results of laboratory screening, results of analysis by the internist, final diagnosis and presence of systemic disease. RESULTS: 149 (44%) patients were examined by the internist, 18 (5.2%) were seen by another specialist. In 169 (49%) patients a specific diagnosis was made. 74 (22%) had a systemic disease, 74 a primary ocular disease. In 28 (8%) a systemic disease was presumed (5% were HLA-B27 positive, 3% had abnormal laboratory results); 5 (1%) patients had endophthalmitis as a complication of a septic process. CONCLUSION: In approximately 1/3 of the patients with uveitis a systemic disease was found. Examination by the internist tailored to the individual patient is essential in the evaluation of uveitis patients.     

Artefactual cleavage of E coli H-NS by OmpT

In the bacterium Escherichia coli, H-NS-(H1, H1a) is a heat-stable protein with a molecular mass of 15.5 kDa involved in nucleoid organisation and gene regulation linked to certain signal transduction pathways. We have shown that, following addition of preparations of everted inner membrane vesicles, heat-stable cleavage products of approximately 10 kDa of H-NS are formed in vitro from newly synthesised, radio-labelled H-NS and from purified H-NS. The 15.5 kDa protein and its cleavage products were also recovered from a minicell system. These results raised the possibility that cleavage of H-NS is physiologically significant. However, the cleavage of H-NS observed appears to occur during cell breakage and to depend on the method of protein extraction and the presence of the outer membrane protease, OmpT. Nevertheless, the results indicate that H-NS may contain at least two separate domains with cleavage occurring between these domains at a preferred OmpT site. Failure to take account of H-NS cleavage in sample preparation and analysis can lead to serious underestimation of H-NS levels.     

Potentiation of the time-dependent, antidepressant-induced changes in the agonistic behaviour of resident rats by the 5-HT1A receptor antagonist, WAY-100635

Acute and chronic antidepressant drug treatments respectively decrease and increase the aggressive behaviour of resident rats during encounters with unfamiliar conspecifics. We have now examined the effect of the 5-hydroxytryptamine1A receptor antagonist, WAY-100635, on fluoxetine-, paroxetine- or venlafaxine-induced changes in aggression. WAY-100635 (0.1 mg/kg), which did not modify behaviour when given alone, potentiated the venlafaxine (5.54 mg/kg)-induced reduction in aggression after acute treatment and, during chronic treatment, accelerated the fluoxetine (0.34 mg/kg/day)-induced increase in aggression, from day 5 to day 2. A similar change in time course was seen with paroxetine (0.33 mg/kg/day), although the increase in aggression was smaller. Venlafaxine (5.54 mg/kg/day, alone or co-administered with WAY-100635) increased aggression by day 2. During chronic treatment, therefore, venlafaxine, at the dose used, had a more rapid onset of action than either fluoxetine or paroxetine, whereas the fluoxetine- and paroxetine-, but not the venlafaxine-, induced increase in aggression was accelerated by WAY-100635. These studies further support the hypothesis that selective blockade of the 5-hydroxytryptamine1A receptor augments the effects of antidepressant drugs in an animal model predictive of antidepressant activity, presumably by concomitant blockade of the somatodendritic 5-hydroxytryptamine1A autoreceptor-mediated negative feedback system of serotonergic neurones.     

Making darkness visible: the discovery of X-ray and its introduction to dentistry

Wilhelm Conrad Roentgen's discovery of the X-ray one century ago has been ranked in importance with the discovery and development of anesthesia and the discovery of microorganisms and their role in disease. Roentgen's scientific devotion and the persistence of C. Edmund Kells, who took Roentgen's discovery and applied it to dentistry, had a great impact on how dentists practice today.     

Outbreak of serogroup C meningococcal disease associated with campus bar patronage

Between February 1991 and April 1992, eight undergraduates at a US residential university and one at a nearby 2-year college contracted serogroup C meningococcal disease. A case-control investigation with 20 controls per case, oropharyngeal carriage surveys, and multilocus enzyme electrophoresis (MEE) of serogroup C isolates were used to identify factors contributing to the outbreak. All eight sterile-site isolates from cases were closely related by MEE and were similar (though not identical) to the strain associated with the 1991-1992 epidemic of meningococcal disease in eastern Canada. Disease was associated with cigarette smoking (p = 0.012), recent patronage of campus-area bars (p = 0.034), estimated amount of time spent in campus-area bars (p = 0.0003), and, especially, recent patronage of one specific bar, bar A (p = 0.0006; odds ratio = 23.1, 95% confidence interval 3.0-571.5). In carriage surveys, 1,528 throat cultures taken from (primarily student) noncases yielded only five (0.3%) strains that were identical by MEE to those from cases. Two of these were found among 22 cultures obtained from bar A employees in spring 1992. Some cases in this outbreak may have followed transmission of the epidemic strain in bar A. Campus bar environments may facilitate the spread of meningococcal disease among teenagers and young adults.     

Information processing deficits associated with developmental coordination disorder: a meta-analysis of research findings

A meta-analysis was conducted to identify information processing factors that characterise children with Developmental Coordination Disorder (DCD). A total of 50 studies yielded 374 effect sizes based on 983 DCD and 987 control children. A mild generalised performance deficit was indicated, since motor-impaired children were inferior on almost all measures of information processing. There were, however, several areas where their deficiencies were more pronounced. The greatest deficiency was in visual-spatial processing. This was evident regardless of whether or not the tasks involved a motor component. Most other deficiencies were in the small-to-moderate range and included kinaesthetic and cross-modal processing. The findings support the notion that perceptual problems, particularly in the visual modality, are associated with difficulties in motor coordination.