Role of sphingosine-1-phosphate (S1P) and the S1P(2) receptor in allergen-induced, mast cell-dependent contraction of rat lung parenchymal strips.

Lung parenchymal strips isolated from ovalbumin-sensitized rats manifest a mast cell-dependent, biphasic contraction when challenged with allergen. The first phase is mediated by the release of preformed 5-HT while the second phase is dependent on de novo synthesis of leukotrienes. Sphingosine 1-phosphate (S1P) is a sphingolipid metabolite which is readily generated in mast cells and has been demonstrated to be an important regulator of allergen-induced mast cell activation. We have used the parenchymal strip to explore the role of sphingosine 1-phosphate and the S1P(2) receptor in the two components of the acute response to allergen. Lung parenchymal strips were prepared from Brown Norway rats actively sensitized to ovalbumin. The strips were set up in organ baths and contractile responses measured isometrically. The inhibitors of sphingosine kinase, D-erythro-NN-dimethylsphingosine (dimethylsphingosine) and 4-[4-(4-chloro-phenyl)-thiazol-2-ylamino]-phenol (SKI-II) inhibited concentration-dependently both phases of the contractile response induced by 0.1 microg ml(-1) ovalbumin. The effects were seen at concentrations similar to those which inhibit the purified enzyme and were selective in that neither the contractile response to adenosine nor that to 5-hydroxytryptamine was affected. JTE-013 (a selective S1P(2) receptor antagonist) also blocked the response to ovalbumin (0.1 microg ml(-1)). However, the concentrations of JTE-013 required (microM) were substantially higher than its affinity for the S1P(2) receptors (nM). However, when tested against a lower concentration of ovalbumin (0.03 microg ml(-1)), JTE-013 inhibited the response with nM potency. These data demonstrate the importance of S1P and the S1P(2) receptor as regulators of allergen-induced activation of mast cells in their natural environment in the rat lung.

The d3-growth hormone (GH) receptor polymorphism is associated with increased responsiveness to GH in Turner syndrome and short small-for-gestational-age children.

CONTEXT: A protein polymorphism of the GH receptor (GHR) based on the genomic deletion of exon 3 (d3-GHR) has recently been linked to the magnitude of growth response to high-dose recombinant human GH (rhGH) therapy of short children without GH deficiency. OBJECTIVE: This study tests the novel association in two distinct groups of rhGH-treated patients, short girls with Turner syndrome and short children born small for gestational age (SGA). DESIGN: The retrospective study included all children who were treated with rhGH during the last 18 yr at our hospital. PATIENTS: Patients with Turner syndrome were defined by the specific karyotype (n = 53), short children born SGA were determined by birth length and/or weight less than -2.0 sd score and a height at start of rhGH therapy less than -2.0 sd score (n = 60). Exclusion criteria were puberty, an age less than 3.5 or more than 14 yr, and GH deficiency. MATERIALS AND METHODS: Growth prediction for the first year of therapy was calculated on the basis of rhGH dose, age, weight, height, and gender-adjusted midparental height according to the prediction models by Ranke et al. The GHR-exon 3 locus was genotyped using a PCR multiplex assay. GH, IGF-I, and IGF binding protein 3 (IGFBP-3) were measured by RIA. INTERVENTION: For growth promotion, a mean rhGH dose of 38 mug/kg.d (sd, +/-8) was administered in Turner syndrome patients and 56 mug/kg.d (sd, +/-11) in short children born SGA. RESULTS: No significant difference in height, spontaneous height velocity, IGF-I, and IGFBP-3 levels was found at the start of rhGH therapy in the three GHR genotype groups studied. At the first year of treatment, girls with Turner syndrome carrying one or two d3-GHR alleles showed a significantly higher increment in height velocity (P = 0.019) and exceeded their growth prediction significantly (P = 0.007), whereas their increments of IGF-I and IGFBP-3, weight, and height were not significantly different. Carriers of d3-GHR in the group of short children born SGA grew significantly faster than predicted (P = 0.023). However, in comparison to the carriers of full-length GHR, gain of height velocity was not significantly higher (P = 0.067). The mean gain of height associated with d3-GHR accounted for approximately 0.75 cm in SGA and 1.5 cm in Turner syndrome during the first year of rhGH therapy. CONCLUSIONS: Our data support the theory that there is increased responsiveness to high-dose rhGH in association with the d3-GHR genotype. The magnitude of this effect may depend on the primary origin of the short stature.

Efficacy of artemether-lumefantrine treatment in patients with acute uncomplicated Falciparum malaria in Mayotte, a French collectivity of the Comoros Archipelago.

Mayotte is a French island located in the Comoros archipelago in the Indian Ocean. Due to the high level of resistance to chloroquine and sulfadoxine-pyrimethamine in this area, new therapeutic strategies are required. The aim was to assess and to document the efficacy of artemether-lumefantrine (AL) combination in four oral dosages. The follow-up was carried out during 21 days to monitor the antimalarial drug efficacy in an open trial in April-May, 2002. Results were obtained from 51 patients, aged from three to 46 years (12% less than five years). No case of therapeutic failure was observed. At day 2 after treatment, all the patients were apyretic and none of them had parasitaemia until day 21. This first therapeutic trial of the AL combination in the Indian Ocean sub-region shows that this association is safe, effective and rapid. AL should be an alternative treatment of uncomplicated malaria attacks in Comoros Archipelago, and will be of help to manage imported chloroquine-resistant falciparum malaria strains in Madagascar.

Inhibition by viozan of extravasation induced in rat trachea by capsaicin is mediated exclusively by beta 2-adrenoceptors.

The mechanism by which 2(3H)-benzothiazolone, 4-hydroxy-7-[2-[[2-[[3-(2-phenylethoxy)propyl]-sulphonyl]ethyl]amino]ethyl]-monohydrochloride (AR-C68397AA; viozan), a dual dopamine D2/beta2-adrenoceptor agonist which has shown promise in the treatment of chronic obstructive pulmonary disease (COPD), inhibits the extravasation of plasma protein induced by capsaicin in the tracheas of Brown Norway rats has been re-evaluated. Viozan (10-30 microg/kg given intratracheally; i.t.) inhibited dose-dependently the extravasation of plasma protein tagged with Evans Blue into rat trachea induced by capsaicin (10 microg/kg i.t.). Similar effects were seen with the selective beta2-adrenoceptor agonist, salbutamol (3-10 microg/kg i.t.), but the selective dopamine D2 receptor agonist, quinagolide (10-30 microg/kg i.t.), was inactive. The effects of viozan and salbutamol were abolished by propranolol (3 mg/kg) given intraperitoneally (i.p.) but unaffected by sulpiride (3 mg/kg i.p.). Thus, in c,ontrast to claims in the literature, a functional response to dopamine D2 receptor activation in a preclinical model of oedema arising from sensory nerve fibre activation in the rat lung could not be demonstrated. Moreover, no qualitative difference could be demonstrated between the response to a dual D2/beta2-adrenoceptor agonist and a selective beta2-adrenoceptor agonist. The observations call into question whether a dual D2/beta2-adrenoceptor agonist such as viozan would bring added benefit over established selective beta2-adrenoceptor agonists in the therapy

Natural porcine surfactant (Curosurf) down-regulates mRNA of tumor necrosis factor-alpha (TNF-alpha) and TNF-alpha type II receptor in lipopolysaccharide-stimulated monocytes.

We have previously shown that Curosurf, a natural porcine surfactant, and its phospholipids effectively suppressed secretion of tumor necrosis factor (TNF-alpha) by resting and through lipopolysaccharide (LPS)-stimulated human monocytes. In this study the effect of Curosurf on monocyte mRNA for TNF-alpha and TNF-alpha type II-receptor (TNF-alpha-RII) were analyzed to evaluate the cellular mechanisms involved in the modulation of TNF-alpha expression. LPS-stimulated monocytes simultaneously exposed to Curosurf (500 microg/mL for 24 h) expressed approximately 70% less TNF-alpha mRNA when compared with control subjects (p < 0.05). In addition, 86% less TNF-alpha RII mRNA was found in monocytes exposed to Curosurf (p < 0.001). Decreased mRNA expression was clearly associated with significantly reduced secretion of TNF-alpha protein (Curosurf-exposed LPS-stimulated monocytes 3628 +/- 1873 pg/mL TNF, LPS-stimulated monocytes 31,376 +/- 2524 pg/mL TNF; mean +/- SEM, p < 0.001). The activation of the transcription factor nuclear factor-kappaB upon LPS stimulation is not affected by Curosurf incubation. This excludes that the decrease in mRNA and protein levels of TNF-alpha and TNF-alpha-RII is due to an inhibition of nuclear factor-kappaB activation by Curosurf. We conclude that Curosurf affects TNF-alpha release of LPS-stimulated monocytes at a pretranslational site by down-regulating both mRNA for TNF-alpha and TNF-alpha-RII, therefore acting as an anti-inflammatory agent within alveolar space.

Isolation and phenotypic characterization of CD117-positive cells.

Mononuclear cells derived from cord blood were stained using the CD1 17-specific, fluorochrome-labeled monoclonal mouse antibody 95C3. Additional staining was performed using an isotype-specific rat-anti-mouse antibody, labeled with supermagnetic microparticles. Target cells were enriched by the technique of magnetic cell separation, MACS. The resulting cell population contained 96.5% (+/-1.7% S.D.) CD1 17-expressing cells (n = 12) with different levels of CD117 antigen expression. Using flow cytometry, two cell populations differing in size were found. A majority (93%) of cells with high forward scatter revealed a phenotype positive for CD117 and CD34. Isolated cells revealed a high fraction of hematopoietic progenitors (16%). The technique presented allows for an alternative approach of stem cell enrichment and might be useful in autologous transplantation of cells with hematopoietic properties.

[Postpericardiotomy syndrome; a rare complication of transcavitary cardiac pacing: apropos of a case]. / Syndrome pleuro-péricardique; une complication rare de la stimulation cardiaque par voie endocavitaire. A propos d'un cas.

The authors report a new case of the post-pericardiotomy syndrome occurring after implantation of a DDD pacemaker. This is a rare complication of the insertion of a screw atrial electrode, the iatrogenic potential of which has already been reported. The immediate outcome was favourable with anti-inflammatory therapy.

Expression of an early myelopoietic antigen (CD33) on a subset of human umbilical cord blood-derived natural killer cells.

A new subset of natural killer (NK) cells was identified in human umbilical cord blood. This subset of CD56+/CD3- NK cells co-expressed the CD33 antigen, which is present on early hematopoietic progenitors confined to the myeloid lineage. The percentage of the CD56+/CD33+ cells among the CD56+/CD3- NK cells was 7.9 +/- 6.6% (n = 27) with a range of 1.4-25.5% and a considerable individual variability. Additionally, the majority of freshly isolated CD56+/CD33+ cells co-expressed the CD2 and CD7 antigen, a minor proportion co-expressed the CD8 antigen but essentially all of the cells stained negative for CD16 and CD57. Morphological analysis of the CD56+/CD33+ cells showed the features of large agranular lymphocytes. From some of the samples, the CD56+/CD33+ NK cells were cultivated and expanded in vitro by incubation of the cells with interleukin 2 (IL-2) for up to 50 days. Morphological analysis of the cultured CD56+/CD33+ cells showed the features of large granular lymphocytes (LGL). The IL-2-expanded CD56+/CD33+ NK cells showed only a low cytolytic activity against K562 target cells, whereas most of the NK activity of the expanded cells was contributed by the CD56+/CD33- NK cells.

[Psychosocial management of deaf patients]. / Psychosoziale Versorgung Gehörloser.

Deaf persons reside in almost all psychiatric hospitals in the Federal Republic, as a recent inquiry has shown. The total population of deaf inmates is probably around 600. These persons have so far not been eligible for treatment specially adapted to their deafness. The present article attempts to stimulate readiness for a specific type of care of such persons. It describes the special psychic stress to which they are exposed in an environment with intact hearing and highlights especially the severe barriers of contact that cannot be overcome by the deaf without assistance from the environment. The subsequent presentation of approaches to the psychosocial care of the deaf is rounded off by a few thoughts on further development.

The physiological surveillance of hemodialysis sessions by the continuous measurement of L.F. impedance of the circulating blood (Thomasset's method).

Everybody grants as a fact that hemodialysis disturbances are produced by volemia variations. During H-D the vascular sector is the necessary transit medium to withdraw excessive interstitial water. If this withdrawing is greater than the coming back of the interstitial water into the vascular sector, the plasmatic volume will be decreasing. Thus, to measure the variations of the plasmatic volume in circulating blood it is sufficient to effect a continuous measurement of these ones in a transducer having a definite volume. So, by the mean of an impedancemeter, 5 kHz impedance is continuously measured between the two electrodes of the transducer, because it is known (Thomasset's method) that at 5 kHz current uses only the plasma in order to pass from one electrode to another.