Effect of histamine,acetylcholine and compound 48/80 on bronchoconstriction and release of eicosanoids in the dog

The effects of Hi and ACH aerosol and of intravenous infusion of compound 48/80 on bronchoconstriction and plasma levels of Hi, TXB₂, KH₂PGF₂ and KH₂PGE₂ were investigated in 11 bastard dogs. Administration of Hi and ACH aerosol induced bronchoconstriction accompanied by an increase in the plasma levels of Hi and TXB₂. No effect on the plasma levels of KH₂PGF₂ and KH₂PGE₂ was detected. Release of endogenous Hi by compound 48/80 induced bronchoconstriction and significant increases in the plasma levels of TXB₂ as well as of KH₂PGF₂ and KH₂PGE₂. The effects of a second administration of Hi and ACH aerosols after compound 48/80 did not differ qualitatively from the effects of the first aerosol administration. However, quantitatively, the second Hi aerosol induced significantly less bronchoconstriction and TXB₂ release. Similarly, effects of the second ACH aerosol tended to be decreased as compared to the first ACH aerosol, although the difference was not significant. The diminished effect of the agonists could be due to receptor desensibilization and/or release of adrenaline, which in turn decreases bronchoconstriction and eicosanoid release.     

Functional insights on the polarized redistribution of leukocyte integrins and their ligands during leukocyte migration and immune interactions

Summary:  Cell–cell and cell–matrix interactions are of critical importance in immunobiology. Leukocytes make extensive use of a specialized repertoire of receptors to mediate such processes. Among these receptors, integrins are known to be of crucial importance. This review deals with the central role of integrins and their counterreceptors during the establishment of leukocyte–endothelium contacts, interstitial migration, and final encounter with antigen-presenting cells to develop an appropriate immune response. Particularly, we have addressed the molecular events occurring during these sequential processes, leading to the dynamic subcellular redistribution of adhesion receptors and the reorganization of the actin cytoskeleton, which is reflected in changes in cytoarchitecture, including leukocyte polarization, endothelial docking structure formation, or immune synapse organization. The roles of signaling and structural actin cytoskeleton-associated proteins and organized membrane microdomains in the regulation of receptor adhesiveness are also discussed.     

Effects of the Ebbinghaus figure on grasping are not only due to misjudged size

It is not evident how the small effects of the flankers of the Ebbinghaus figure on peak grip aperture (PGA) should be interpreted. One interpretation is that the flankers influence the estimated size, which in turn influences the grasp. If this interpretation is correct, then only the size-dependent aspects of the grasping movement should depend on the spatial positions of the flankers. An alternative interpretation is that the effect on grip aperture is caused by a change in judgement of the required precision, in which case various aspects of the grasping movement could be influenced by the size and position of the flankers. We presented subjects with a display consisting of a central disk surrounded by four large or small flankers. The array of circular flankers could be rotated by 45°. There were two tasks: to reproduce the perceived size of the central disk, and to grasp the central disk. As in other studies, the reproduced size and the PGA were both influenced by the size of the flankers. The effect on reproduced size settings was independent of the flankers spatial position. Nevertheless, the flankers position did influence the final grip aperture and the grip orientation at PGA and at movement offset. Because the flankers changed more than only the PGA, we conclude that the effect of the flankers on prehension cannot only be because of misjudgement of the size of the central disk.     

Superior cycle control with a contraceptive vaginal ring compared with an oral contraceptive containing 30 microg ethinylestradiol and 150 microg levonorgestrel: a randomized trial

BACKGROUND: This trial was conducted to compare cycle control with vaginal ring a combined contraceptive vaginal ring, and a combined oral contraceptive (COC) delivering 30 mug ethinylestradiol (EE) and 150 mug levonorgestrel. METHODS: This open-label, randomized, multi-centre, Phase III study involved adult women from 11 countries. Subjects were treated with either vaginal ring or a COC for 13 cycles (12 months). RESULTS: A total of 1030 subjects (vaginal ring, n=512; COC, n=518) comprised the intention-to-treat (ITT) population. The percentage of women in the ITT population who completed the trial was 70.9% for vaginal ring and 71.2% for the COC group. The incidence of breakthrough bleeding and spotting over cycles 2-13, the primary efficacy parameter, was lower with vaginal ring (range 2.0-6.4%) than the COC (range 3.5-12.6%), and for cycles 2 and 9 the lower incidence with vaginal ring was confirmed as statistically significant (P=0.003 and P=0.002 respectively). The incidence of intended bleeding was significantly higher over all cycles with vaginal ring (58.8-72.8%) than with the COC (43.4-57.9%). CONCLUSIONS: Cycle control with vaginal ring was excellent and superior to that of a COC containing 30 mug EE.     

Trends in drug resistance, serotypes, and molecular types of Streptococcus pneumoniae colonizing preschool-age children attending day care centers in Lisbon, Portugal: a summary of 4 years of annual surveillance

Of the nasopharyngeal cultures recovered from 942 day care center (DCC) attendees in Lisbon, Portugal, 591 (62%) yielded Streptococcus pneumoniae during a surveillance performed in February and March of 1999. Forty percent of the isolates were resistant to one or more antimicrobial agents. In particular, 2% were penicillin resistant and 20% had intermediate penicillin resistance. Multidrug resistance to macrolides, lincosamides, and tetracycline was the most frequent antibiotype (17% of all isolates). Serotyping and molecular typing by pulsed-field gel electrophoresis were performed for 202 out of 237 drug-resistant pneumococci (DRPn). The most frequent serotypes were 6B (26%), 14 (22%), 19F (16%), 23F (10%), and nontypeable (12%). The majority (67%) of the DRPn strains were representatives of nine international clones included in the Pneumococcal Molecular Epidemiology Network; eight of them had been detected in previous studies. Fourteen novel clones were identified, corresponding to 26% of the DRPn strains. The remaining 7% of the strains were local clones detected in our previous studies. Comparison with studies conducted since 1996 in Portuguese DCCs identified several trends: (i) the rate of DRPn frequency has fluctuated between 40 and 50%; (ii) the serotypes most frequently recovered have remained the same; (iii) nontypeable strains appear to be increasing in frequency; and (iv) a clone of serotype 33F emerged in 1999. Together, our observations highlight that the nasopharynxes of children in DCCs are a melting pot of successful DRPn clones that are important to study and monitor if we aim to gain a better understanding on the epidemiology of this pathogen.     

Autoimmunity and inflammation due to a gain-of-function mutation in phospholipase C gamma 2 that specifically increases external Ca2+ entry

The identification of specific genetic loci that contribute to inflammatory and autoimmune diseases has proved difficult due to the contribution of multiple interacting genes, the inherent genetic heterogeneity present in human populations, and a lack of new mouse mutants. By using N-ethyl-N-nitrosourea (ENU) mutagenesis to discover new immune regulators, we identified a point mutation in the murine phospholipase Cg2 (Plcg2) gene that leads to severe spontaneous inflammation and autoimmunity. The disease is composed of an autoimmune component mediated by autoantibody immune complexes and B and T cell independent inflammation. The underlying mechanism is a gain-of-function mutation in Plcg2, which leads to hyperreactive external calcium entry in B cells and expansion of innate inflammatory cells. This mutant identifies Plcg2 as a key regulator in an autoimmune and inflammatory disease mediated by B cells and non-B, non-T haematopoietic cells and emphasizes that by distinct genetic modulation, a single point mutation can lead to a complex immunological phenotype.     

Presence of the cfxA gene in Bacteroides distasonis

In this study we investigated the presence of the cfxA gene (encoding a class A beta-lactamase) in 73 strains of the Bacteroides fragilis group belonging to the species B. distasonis (34), B. vulgatus (14), B. thetaiotaomicron (8), B. merdae (6), B. caccae (9) and B. ovatus (2) isolated from human intestinal microflora of healthy children and adults. Employing specific primers to the cfxA gene, a 312-bp amplified fragment was obtained in 2 strains of B. vulgatus and 9 strains, the majority from children, of B. distasonis. The expression of this enzyme was analysed by determining the MICs to cefoxitin and cefotaxime and values varied from 2 to >256 microg/ml of both cefoxitin and cefotaxime. Sequence analysis of the amplicons corresponding to the cfxA gene from B. distasonis and B. vulgatus revealed identical sequences between these isolates and high similarity with other beta-lactamase genes of anaerobes such as cfxA of B. vulgatus (99%) and cfxA2 of Prevotella intermedia (99%), both sequences of which deposited in Genbank under accession numbers U38243 and AF118110, respectively. However, a fragment obtained from a B. distasonis strain (EC17-4) showed a unique RFLP profile and 87% nucleotide similarity with cfxA and cfxA2 genes. These results seem to suggest a dissemination of these resistance determinants among Bacteroides species.     

Timing of bimanual movements in human and non-human primates in relation to neuronal activity in primary motor cortex and supplementary motor area

It has been established that repeated presentation of a transient target motion stimulus such as a constant-velocity ramp leads to the build up of steady state (SS), anticipatory smooth pursuit eye movements after two or three presentations. Each SS response is then composed of the anticipatory component of nonvisual origin, a visual component associated with the stimulus presentation and another nonvisual component that represents the decay of the response after extinction of the stimulus. Here we investigated the interactions that occur when each motion stimulus was itself a sequence containing more than one ramp component. Ramp components had a velocity of 15 degrees /s or 30 degrees /s to left or right and were separated by gaps of 200 ms duration. In an initial experiment, responses to 2-ramp stimuli were examined and compared with responses to the single-ramp stimuli from which they were constituted. We present evidence that the anticipatory, nonvisual components of the double-ramp response result from the linear summation of the nonvisual components of the responses to the constituent single-ramp components. In a 2nd experiment, we examined responses to a wide variety of 4-ramp sequences and again found evidence that, in the SS, the responses were formed from the linear summation of the constituent single-ramp components. Regression analysis performed on the velocity at onset of each ramp component indicated that this nonvisual part of the response was predictive of the upcoming ramp component. To confirm this, unexpected changes were introduced into single ramp components of the 4-ramp sequence after at least five prior presentations of the sequence had allowed a SS response to be established. Subjects continued to initiate a response to the modified component that was appropriate in velocity and direction for the corresponding part of the previous sequence and inappropriate for the newly modified stimulus. This preprogrammed response persisted unmodified for more than 170 ms after onset of the modified ramp component. In contrast, in the second presentation of the new sequence, the anticipatory component of the response was highly correlated with the SS response of the new sequence, but not with that of the prior sequence, showing that the preprogrammed response had been modified very rapidly. Similar behaviour was observed whichever of the 4-ramp components was modified, indicating that the velocity and direction of the anticipatory response to each component had been preprogrammed. The results suggest that velocity information related to at least four elements of a sequence can be temporarily stored and subsequently released with appropriate temporal order to form an anticipatory response throughout the whole sequence.