Perturbation and proinflammatory type activation of V delta 1(+) gamma delta T cells in African children with Plasmodium falciparum malaria

gamma delta T cells have variously been implicated in the protection against, and the pathogenesis of, malaria, but few studies have examined the gamma delta T-cell response to malaria in African children, who suffer the large majority of malaria-associated morbidity and mortality. This is unfortunate, since available data suggest that simple extrapolation of conclusions drawn from studies of nonimmune adults ex vivo and in vitro is not always possible. Here we show that both the frequencies and the absolute numbers of gamma delta T cells are transiently increased following treatment of Plasmodium falciparum malaria in Ghanaian children and they can constitute 30 to 50% of all T cells shortly after initiation of antimalarial chemotherapy. The bulk of the gamma delta T cells involved in this perturbation expressed V delta 1 and had a highly activated phenotype. Analysis of the T-cell receptors (TCR) of the V delta 1(+) cell population at the peak of their increase showed that all expressed V gamma chains were used, and CDR3 length polymorphism indicated that the expanded V delta 1 population was highly polyclonal. A very high proportion of the V delta 1(+) T cells produced gamma interferon, while fewer V delta 1(+) cells than the average proportion of all CD3(+) cells produced tumor necrosis factor alpha. No interleukin 10 production was detected among TCR-gamma delta(+) cells in general or V delta 1(+) cells in particular. Taken together, our data point to an immunoregulatory role of the expanded V delta 1(+) T-cell population in this group of semi-immune P. falciparum malaria patients.     

Blood lactate response to overtraining in male endurance athletes

Many physiological markers vary similarly during training and overtraining. This is the case for the blood lactate concentration ([La⁻]_b), since a right shift of the lactate curve is to be expected in both conditions. We examined the possibility of separating the changes in training from those of overtraining by dividing [La⁻]_b by the rating of perceived exertion ([La⁻]_b/RPE) or by converting [La⁻]_b into a percentage of the peak blood lactate concentration ([La⁻]_b,peak). Ten experienced endurance athletes increased their usual amount of training by 100% within 4 weeks. An incremental test and a time trial were performed before (baseline) and after this period of overtraining, and after 2 weeks of recovery (REC). The [La⁻]_b and RPE were measured during the recovery of each stage of the incremental test. We diagnosed overtraining in seven athletes, using both physiological and psychological criteria. We found a decrease in mean [La⁻]_b,peak from baseline to REC [9.64 (SD 1.17), 8.16 (SD 1.31) and 7.69 (SD 1.84) mmol · l⁻¹, for the three tests, respectively; P < 0.05] and a right shift of the lactate curve. Above 90% of maximal aerobic speed (MAS) there was a decrease of mean [La⁻]_b/RPE from baseline to REC [at 100% of MAS of 105.41 (SD 17.48), 84.61 (SD 12.56) and 81.03 (SD 22.64) arbitrary units, in the three tests, respectively; P < 0.05), but no difference in RPE, its variability accounting for less than 25% of the variability of [La⁻]_b/RPE (r=0.49). Consequently, [La⁻]_b/RPE provides little additional information compared to [La⁻]_b alone. Expressing [La⁻]_b as a %[La⁻]_b,peak resulted in a suppression of the right shift of the lactate curve, suggesting it was primarily the consequence of a decreased production of lactate by the muscle. Since the right shift of the curve induced by optimal training is a result of improved lactate utilization, the main difference between the two conditions is the decrease of [La⁻]_b,peak during overtraining. We propose retaining it as a marker of overtraining for long duration events, and repeating its measurement after a sufficient period of rest to make the distinction with overreaching. Accepted: 26 September 2000     

Presence and mechanism of macrolide-lincosamide resistance in Enterococcus columbae strains belonging to the intestinal flora of pigeons.

Faecal samples from 50 pigeons all originating from different lofts were screened for the presence of macrolide and lincosamide (ML)-resistant isolates of Streptococcus gallolyticus and Enterococcus columbae by plating the samples onto selective media. Sixty-eight ML-resistant E. columbae strains were recovered from the faecal samples of 29 animals. Two of these samples also harboured ML-resistant S. gallolyticus strains. The erm(B) gene was detected in 58 E. columbae and in five S. gallolyticus isolates. Four of these E. columbae isolates also carried the mef(A) gene. Five E. columbae strains possessed the mef(A) gene in the absence of erm(B). On the basis of the sequence of the complete erm(B) gene, 10 E. columbae isolates clustered together in six groups. In two of these isolates, the erm(B) gene sequence was identical to that of S. gallolyticus strains, indicating that exchange of resistance genes might occur between pathogenic and non-pathogenic bacterial species belonging to the pigeon's intestinal flora.     

Thymocyte expression of cathepsin L is essential for NKT cell development

CD1d antigen presentation to natural killer T (NKT) cells expressing the semi-invariant T cell receptor V(alpha)14J(alpha)18 requires CD1d trafficking through endosomal compartments; however, the endosomal events remain undefined. We show that mice lacking the endosomal protease cathepsin L (catL) have greatly reduced numbers of V(alpha)14(+)NK1.1(+) T cells. In addition, catL expression in thymocytes is critical not only for selection of these cells in vivo but also for stimulation of V(alpha)14(+)NK1.1(+) T cells in vitro. CD1d cell-surface expression and intracellular localization appear normal in catL-deficient thymocytes, as does the lysosomal morphology; this implies a specific role for catL in regulating presentation of natural CD1d ligands mediating V(alpha)14(+)NK1.1(+) T cell selection. These data implicate lysosomal proteases as key regulators of not only classical major histocompatibility complex class II antigen presentation but also nonclassical CD1d presentation.     

Trisomy 7 mosaicism, maternal uniparental heterodisomy 7 and Hirschsprung's disease in a child with Silver-Russell syndrome

Prenatal trisomy 7 is usually a cell culture artifact in amniocytes with normal diploid karyotype at birth and normal fetal outcome. In the same way, true prenatal trisomy 7 mosaicism usually results in a normal child except when trisomic cells persist after birth or when trisomy rescue leads to maternal uniparental disomy, which is responsible for 5.5-7% of patients with Silver-Russell syndrome (SRS). We report here on the unusual association of SRS and Hirschsprung's disease (HSCR) in a patient with maternal uniparental heterodisomy 7 and trisomy 7 mosaicism in intestine and skin fibroblasts. HSCR may be fortuitous given its frequency, multifactorial inheritance and genetic heterogeneity. However, the presence of the trisomy 7 mosaicism in intestine as well as in skin fibroblasts suggests that SRS and HSCR might possibly be related. Such an association might result from either an increased dosage of a nonimprinted gene due to trisomy 7 mosaicism in skin fibroblasts (leading to SRS) and in intestine (leading to HSCR), or from an overexpression, through genomic imprinting, of maternally expressed imprinted allele(s) in skin fibroblasts and intestine or from a combination of trisomy 7 mosaicism and genomic imprinting. This report suggests that the SRS phenotype observed in maternal uniparental disomy 7 (mUPD(7)) patients might also result from an undetected low level of trisomy 7 mosaicism. In order to validate this hypothesis, we propose to perform a conventional and molecular cytogenetic analysis in different tissues every time mUPD7 is displayed.     

Failure to obtain a unique threshold on the blood lactate concentration curve during exercise

The purpose of this study was to compare various methods and criteria used to identify the anaerobic threshold (AT), and to correlate the AT obtained with each other and with running performance. Furthermore, a number of additional points throughout the entire range of lactate concentrations [La^?] were obtained and correlated with performance. A group of 19 runners [mean age 33.7 (SD 9.6) years, height 173 (SD 6.3) cm, body mass 68.3 (SD 5.4)?kg, maximal O₂ uptake (V˙O_{2 max} ) 55.2 (SD 5.9)?ml?·?kg^?1?·?min^?1] performed a maximal multistage treadmill test (1?km?·?h^?1 every 3.5?min) with blood sampling at the end of each stage while running. All AT points selected (visual [La^?], 4?mmol?·?l^?1 [La^?], 1?mmol?·?l^?1 above baseline, log-log breakpoint, and 45° tangent to the exponential regression) were highly correlated one with another and with performance (r?>?0.90) even when there were many differences among the AT (P??1 [La^?], 1 to 6?mmol?·?l^?1 [La^?] above the baseline, and 30 to 70° tangent to the exponential curve of [La^?]) were also highly correlated with performance (r?>?0.90). These results failed to demonstrate a distinct AT because many points of the curve provided similar information. Intercorrelations and correlations between AT and performance were, however, reduced when AT were expressed as the percentage of maximal treadmill speed obtained at AT or percentage of V˙O_{2 max} . This would indicate that different attributes of aerobic performance (i.e. maximal aerobic power, running economy and endurance) are measured when manipulating units. Thus, coaches should be aware of these results when they prescribe an intensity for training and concentrate more on the physiological consequences of a chosen [La^?] rather than on a “threshold”.     

Identification, in mouse macrophages and in serum, of a soluble receptor for the Fc portion of IgG (Fc{gamma}R) encoded by an alternatively spliced transcript of the Fc{gamma}RII gene

Low affinity FcR are a heterogeneous group of glycoproteinswhich exist in transmembrane (TM) as well as in soluble forms.Two membrane isoforms of the murine type II FcR, FcRilb1 andFc;Rilb2, have been described. They result from the translationof alternatively spliced premRNA, FcRilb2 lacking sequencesof the first intracytoplasmic domain (IC1). Soluble forms ofFcR (sFcR) have previously been shown to result from proteolysisof membrane receptors. We report here the identification, inmacrophages, of a mRNA derived from the FCRll gene by splicingexons encoding the TM and IC1 domains, i.e. corresponding toa TM-deleted FcRllb2 mRNA. A soluble protein possibly encodedby this mRNA was identified in macrophage supernatants. In accordancewith FcR nomenclature, we propose to name this new FcRll IsoformFcRllb3. It is the most abundant 8FcR present in serum, as comparedwith 8FcR resulting from cleavage of membrane FcR.