Interactions between peripheral blood CD8 T lymphocytes and intestinal epithelial cells (iEC)

Intestinal intraepithelial lymphocytes (iIEL) are primarily CD8 cells and most of them have a CD28^? phenotype, the phenotype of effector cytotoxic T cells. We asked whether the predominance of CD8⁺ CD28^? T cells in the gut may result from peripheral blood T cells preferentially migrating to the iIEL compartment and adhering to iEC. Compared with CD4 cells, adhesion of resting CD8⁺ T cells to iEC cell lines was significantly higher. Adhesion could be blocked with a MoAb to gp180, a molecule expressed on iEC which is known to interact with CD8/lck. No significant difference in the level of adhesion was observed between CD8⁺ CD28⁺ and CD8⁺ CD28^? T cells. Thus CD8 cells may preferentially migrate to the iIEL compartment, but loss of CD28 expression could occur in situ after migration. Consistent with this hypothesis, the CD8⁺ CD28^? cells became enriched after co-culturing T cells with iEC cell lines and primary iEC. Induction of the CD8⁺ CD28^? phenotype in cord blood and adult T cells was observed in co-cultures with iEC and also with mitogens and superantigens. In the latter case, CD28 down-modulation was seen specifically in the Vβ subset targeted by the superantigen, indicating that loss of CD28 expression is a direct result of T cell receptor (TCR)-mediated stimulation. The combined results suggest that CD8⁺ CD28^? T cells are antigen experienced T cells, and that they may have a survival advantage in the presence of gut epithelial cells in vitro. This may contribute to the predominance of CD8⁺ CD28^? T cells in the iIEL compartment.     

The decay of house dust mite allergens, Der p I and Der p II, under natural conditions

Background: Fluctuations in the level of mite allergens in domestic house dust are the result of changes in the balance between synthesis, removal and decay. Purely physical forces as well as enzymatic degradation, mediated by house dust inhabiting microbes, may contribute to the decay of allergens in domestic dust. Knowledge about the speed of decay is essential for an understanding of the dynamics of allergen levels. Objective: The present study is a quantitative assessment of the speed of decay at nine combinations of temperature (15°C, 20°C and 25°C) and relative humidity (33%, 55% and 75%). Methods: Samples of mite infested material of an old rug were stored at these temperature/relative humidity-combinations for 6, 12 or 18 months, after the mites were killed by cither a freezing treatment or an acaricide (lindane). The microbes living in the rug presumably survive these treatments. Concentrations of Der p I and Der p II + Der f II. in extracts of the rug material, were measured by a radio immunoassay. Results: No significant changes in the levels of Der p I and Der p II +Der f II, could be detected even after 1¹/₂ year at a high temperature and humidity. Conclusion: These findings incidate that mite allergens can be extremely stable under normal domestic circumstances.     

Computer simulation of the occlusal anatomy of the first mandibular molar after varying the determinants of mandibular movement in the CICERO CAD/CAM system

Static and dynamic occlusal interferences often occur in restorations. The CICERO CAD/CAM technique was used to control the occlusal dimensions of all‐ceramic restorations by setting the variables which determine the mandibular contact movements. The anatomy of the occlusal form of the (pre)molar teeth is influenced by the setting of the sagittal and transversal determinants of mandibular contact movements. In this study the variation in occlusal morphology of a high‐ and low‐limit setting of six variables was compared with an averaged setting. The settings (high, low and averaged, respectively) of the mandibular movement: the sagittal condylar (60°, 0°, 30°) and the incisal guide angle (60°, 0°, 30°) as well as the long centric articulation (1·2 mm, 0 mm, 0·6 mm) influence mainly the antero‐posterior direction, whereas the settings of Bennett movement (laterotrusion: 30°, 0°, 15°), Bennett side shift (laterotranslation: 1, 0, 0·5 mm) and the wide centric (lateral intercuspal contact area: 0·6, 0, 0·3 mm) will mainly influence the transversal direction of the mandibular movement. The influence of the variation of settings on ‘dynamic’ crown morphology as compared with the static crown morphology was studied by comparison of mesio‐distal and bucco‐lingual sections at the same occlusal position of the first lower molar design. Furthermore, the amount of material needed for the correction of the ‘static’ crown to avoid interferences in dynamic conditions was calculated. It appeared that most correction was needed for the ipsilateral settings: Bennett side shift (1·0 mm), Bennett movement (30°) and the Sag. Condylar guidance (0°) as well as the Incisal angle (0°), which could be studied in the bucco‐lingual sections. Also the Bennett side shift on the contra‐lateral side influenced the occlusal contour strongly, which could be seen in the mesio‐distal section. It was concluded that simulation of the influence of several types of determinants of mandibular movement on the three‐dimensional occlusal anatomy can be studied using the CICERO‐CAD/CAM technique. The ipsi‐ and contralateral Bennett side shift variation influenced the occlusal anatomy more than other variables.     

Atrioventricular Node Ablation for Optimization of Pacemaker Treatment in Hypertrophic Obstructive Cardiomyopathy

Dual chamber pacing is a new indication for the treatment of drug resistant hypertrophic obstructive cardiontyopathy (HOCM) in patients with normal atrioventricular (AV) conduction. In sinus rhythm, the efficacy of the treatment is mainly related to the ability to bypass the normal AV conduction system in order to obtain a complete and permanent right ventricular (RV) capture. This is achieved by programming short AV delays. On the other hand, patients with HOCM frequently have co-existing left ventricular diastolic dysfunction, and the atrial contribution to left ventricular filling is critical. The lack of improvement, rarely encountered, is probably due to incomplete RV capture andlor to the deleterious effect of short AV delay. Instrumental AV node prolongation may he indicated in this situation. This procedure should be undertaken when previous drug-induced AV prolongation has failed. In theory, AV node modulation (i.e., creating a I ± AV block) seems ideal. However, this technique remains difficult, with disappointing chronic results. Most authors hence perform "conventional" AV node ablation. Particular attention is taken in order to perform a proximal node ablation, resulting in a complete AV block with narrow QRS escape rhythm. The reported incidence of AV node prolongation ranges from 7.5%-37.5%. The efficacy of the procedure on symptoms is explained by improved left ventricular filling and/or a further reduction in the systolic gradient evoked by complete RV capture. Another indication for AV node ablation in HOCM is the occurrence of atrial fibrillation, in order to restore adequate and permanent RV capture .     

Trypsin-mediated semisynthesis of salmon calcitonin

Salmon calcitonin, CT(1-32)·NH₂, was synthesised by the trypsin-mediated coupling of the peptide fragments CT(1-24) and CT(25-32)·NH₂, prepared by conventional Fmoc solid-phase chemistry. Optimal conditions regarding reaction time course, pH, proportion of catalyst, substrate concentration and composition of the reaction medium were determined from initial studies on the coupling of CT(1-11) to CT(12-24) and of CT(12-24) to CT(25-32)·NH₂. For the final successful semisynthesis, we found that it was unnecessary to protect lysine residues not involved in the coupling, and that secondary hydrolysis at these sites could be prevented by increasing the pH of the reaction medium. The reaction achieved equilibrium after 30-45 min, with overall conversion of around 30% of the initial amount of CT(1-24) substrate into product. Yields were depressed due to cyclisation of the CT(1-24) substrate via air-oxidation of the Cys¹ and Cys⁷ residues.     

Effect of oral and inhaled cetirizine in allergen induced bronchoconstriction

Cetirizine is a potent, selective H₁ histamine receptor antagonist. The effect of oral and inhaled eetirizine was assessed on the early bronchoconstrictor response to inhaled allergen in 10 mild atopie asthmatic patients in a double-blind, randomized, plaeebo controlled trial. All were sensitive to Dermatophagoides pleronyssinus and this was used as the provoking allergen. The geometric mean PD20 FEV] values obtained at allergen challenge were measured as cumulative breath units (c.b.u.) and following oral cetirizine, inhaled cetirizine and placebo were 124–5, 75–7 and 76–7 c.b.u. respectively. These did not differ significantly. We conclude that neither oral nor inhaled cetirizine significantly attenuates the early response to inhaled allergen in atopie asthmatic subjects. However, the method of repeated allergen challenge is likely to be relatively insensitive. Clinical and Experimental Allergy, [o]. 23, pp. 528–531.     

The influence of anaesthetic techniques and type of delivery on peripartum serum interleukin-6 concentrations

Background: Interleukin-6 is a pleiotropic cytokine with a wide range of physiological activities. It plays an important role in the immuno-neuro-humoral axis during stress and surgery.
Methods: Serum interleukin-6 in parturients was measured on hospital admission, immediately after birth and 12 and 24 hours later. All parturients had uncomplicated pregnancies, and delivered vaginally without (n=31) or with (n=20) epidural analgesia, or underwent Caesarean section under epidural (n=20) or general (n=10) anaesthesia.
Results: Serum interleukin-6 assayed immediately following Caesarean section was low, but peaked 12 hours later, irrespective of the anaesthetic technique or other foetomaternal characteristics. Patients who delivered vaginally showed the highest interleukin-6 levels immediately after delivery. These were positively correlated with serum interleukin-6 on admission and duration of labour. Serum interleukin-6 was significantly higher in parturients who had epidural analgesia, and was significantly lower in those receiving intravaginal prostaglandins compared to those without prostaglandins.
Conclusion: The interleukin-6 response after Caesarean section can be explained by a generalized acute phase response to surgery, with no anaesthetic, maternal or neonatal interference. The rapid increase in peripartum serum interleukin-6 levels after vaginal delivery reflects, in part, cervical ripening or labour, their physiological triggers and psychological or physical stress. Regional anaesthesia, duration of labour and exogenous prostaglandin administration can modulate the peripartum interleukin-6 response and subsequently the physiological effects of this cytokine.     

Studies on the relationship between transaldolase activity and testosterone synthesis in Leydig cells of pubertalmice

Objective: To study the relationship between transaldolase activity, protein expression and testosterone synthesis in Leydig cells of pubertal mice. Methods: Leydig cells were cultured for 2 hours and 8 hours, to the Stimulation Group, hCG was added and to the Controls, only the vehicle. The testosterone concentration was then determined by enzyme-linked immunoadsordent assay (ELISA) and the transaldolase activity and protein expression by Western blot. Results: (1) Both the testosterone concentration and the transaldolase activity in both Stimulation Groups were significantly higher than those in the corresponding Controls (2 h: p<0.05-0.01; 8 h: P<0.001); (2) The ratios of the A isoform, the B isoform and the total transaldolase protein to β-actin between the Stimulation and Control Groups did not differ signifi-cantly. Conclusion: hCG stimulates the transaldolase activity as well as the testosterone synthesis in the Leydig cells of pubertal mice, indicating a positive relationship between them.