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1.
Different modulation by histamine of IL-4 and interferon-gamma (IFN-γ) release according to the phenotype of human Th0, Th1 and Th2 clones
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Histamine, an important inflammatory mediator in allergic diseases and asthma, has been reported to have modulator effects on T cells, suggesting that the bronchial microenvironment may regulate the function of resident T cells. We examined the effect of histamine on the release of the Th2-associated cytokines IL-4 and IL-5 and the Th1-associated cytokine IFN-γ by 30 CD4+ T cell clones from peripheral blood or bronchial biopsy of one atopic subject. Based on the IL-4/IFN-γ ratio, the clones were ascribed to the Th2 (ratio >1), Th0 (ratio 0.1 and 1) or Th1 (ratio <0.1) phenotype. Histamine inhibited IFN-γ production by Th1-like cells (P<0.02, Kruskall–Wallis), especially from bronchial biopsy, but had no effect on IL-4 release. Regarding Th0 clones, histamine inhibited IL-4 production (P<0.02) in a dose-dependent manner and slightly inhibited IFN-γ production, but had no effect on Th2-like cells. Histamine had a heterogeneous and insignificant effect on IL-5 production. The H2-receptor antagonist ranitidine completely reversed the inhibition of IL-4 and IFN-γ production, whereas the agonist dimaprit mimicked this effect. In contrast, H1- and H3-receptor agonists and antagonists had no significant effect. These data demonstrate that histamine has different effects on IL-4 and IFN-γ release by T helper cells according to their phenotype via H2-receptors. This study extends the immunomodulatory effects of histamine which may contribute to the perpetuation of airway inflammation in asthma. 相似文献
2.
The role of size, sequence and haplotype in the stability of FRAXA and FRAXE alleles during transmission 总被引:2,自引:5,他引:2
Murray A; Macpherson JN; Pound MC; Sharrock A; Youings SA; Dennis NR; McKechnie N; Linehan P; Morton NE; Jacobs PA 《Human molecular genetics》1997,6(2):173-184
Factors involved in the stability of trinucleotide repeats during
transmission were studied in 139 families in which a full mutation,
premutation or intermediate allele at either FRAXA or FRAXE was
segregating. The transmission of alleles at FRAXA, FRAXE and four
microsatellite loci were recorded for all individuals. Instability within
the minimal and common ranges (0-40 repeats for FRAXA, 0-30 repeats for
FRAXE) was extremely rare; only one example was observed, an increased in
size at FRAXA from 29 to 39 repeats. Four FRAXA and three FRAXE alleles in
the intermediate range (41-60) repeats for FRAXA, 31-60 for FRAXE) were
unstably transmitted. Instability was more frequent for FRAXA intermediate
alleles that had a tract of pure CGG greater than 37 although instability
only occurred in two of 13 such transmissions: the changes observed were
limited to only one or two repeats. Premutation FRAXA alleles over 100
repeats expanded to a full mutation during female transmission in 100% of
cases, in agreement with other published series. There was no clear
correlation between haplotype and probability of expansion of FRAXA
premutations. Instability at FRAXA or FRAXE was more often observed in
conjunction with a second instability at an independent locus suggesting
genomic instability as a possible mechanism by which at least some FRAXA
and FRAXE mutations arise.
相似文献
3.
Van Der Hulst RR Deutz NE Von Meyenfeldt MF Elbers JM Stockbrügger RW Soeters PB 《Clinical nutrition (Edinburgh, Scotland)》1994,13(4):228-233
A diminished glutamine delivery by peripheral tissues is suggested to play an important role in the etiology of postoperative complications of nutritionally depleted patients. Decreased glutamine supply to the gut mucosa in these nutritionally depleted patients may have important consequences for the integrity of the gut mucosa barrier. To evaluate whether glutamine concentration in the gut mucosa of depleted patients is altered, patients with either a fat-free mass index below 90% or percentage ideal body weight below 90% as a result of weight loss were studied. 22 patients admitted to the University Hospital Maastricht and 14 controls were studied. After an overnight fast, venous blood was sampled and duodenal biopsies were obtained by endoscopy. Plasma and tissue amino acids were measured. Fat-free mass was determined by bioelectrical impedance measurement. In 10 depleted patients glutamine concentration in the duodenal mucosa was 2883 +/- 250 mumol/kg dry weight. Concentration of alanine was 2570 +/- 263 mumol/kg dry weight. In the non-depleted patients glutamine and alanine concentrations were respectively 3463 +/- 171 mumol/kg dry weight and 3540 +/- 315 mumol/kg dry weight. Concentrations in controls were 3296 +/- 176 mumol/kg dry weight for glutamine and 3682 +/- 372 mumol/kg dry weight for alanine. Concentrations for alanine and glutamine were significantly lower in depleted patients compared to non-depleted patients (p < 0.05). Also, alanine and glutamine concentrations were significantly correlated with percentage ideal body weight (r=0.43, p < 0.005 for glutamine and r=0.62, p < 0.001 for alanine) and fat-free mass index (r=0.42, p < 0.05 for glutamine and r=0.48, p < 0.01 for alanine) This study suggests that in patients depletion appears to be related to decreased plasma and mucosa glutamine and alanine concentrations. 相似文献
4.
Dietary protein given as pre-digested protein improves the nutritional value of the meal. However, studies measuring absorption kinetics of pre-digested protein or free amino acid mixtures are scarce and suffer from methodological problems. Therefore, the study was designed to study whether differences in absorption kinetics play a role. The kinetics of substrate production or consumption after a rapid gastrically-infused meal was studied across the portal drained viscera, liver and hindquarter in conscious, multicatheterized healthy pigs of 20-22 kg (n = 12). The meal contained carbohydrates and protein (1.44 g/kg body weight) as intact whey protein isolate, moderately-hydrolyzed protein digest or equivalent amino acid mixture (including glutamine and asparagine). For almost all amino acids and glucose, intestinal production, liver and hindquarter uptake were similar.The higher liver urea production (less than 15% of total alpha-amino intake) after the meals with pre-digested protein or free amino acids was related to the marginally higher intestinal glutamine breakdown (not significant) and ammonia production. Our results suggest that in the normal healthy pig, uptake and metabolism of moderately hydrolyzed,free amino acid or intact protein meals with identical composition is not different. 相似文献
5.
Dejong CH Olde Damink SW Deutz NE Soeters PB 《Clinical nutrition (Edinburgh, Scotland)》1996,15(3):149-50; author reply 150
6.
7.
HABIB BOUKERCHE MARIE-HéLèNE RUCHAUD-SPARAGANO CHRISTINE R OUEN JEAN BROCH IER CéCILE KAPLAN & JOHN LOUIS MCGREGOR 《British journal of haematology》1996,92(2):442-451
P-selectin (also called CD62, GMP-140, PADGEM, CD62P) is a recently described member of a family of vascular adhesion receptors expressed by activated platelets and endothelial cells that are involved in leucocyte cell adhesion. The aim of this study was to characterize a new monoclonal antibody (LYP7) directed against activated human blood platelets that inhibits ristocetin-induced platelet aggregation. Immunoadsorbent affinity chromatography and immunoprecipitation studies showed that LYP7 (IgG1) bound a surface-labelled glycoprotein (GP) which changed its apparent molecular mass (Mr) on reduction from 138 kD (situated below GPIIb) to 148 kD (above GPIIbα). LYP7 and S12, a monoclonal antibody directed against P-selectin immunoprecipitated the same band. Using ELISA assay, purified P-selectin was shown to bind LYP7 and S12 monoclonal antibodies. Binding sites of 125I-labelled LYP7, which was greatly increased on thrombin-stimulated (2 U/ml) washed platelets (10825±2886, mean ±SD) (Kd=1.5±0.5 nm ) compared to resting platelets (2801±1278, mean ±SD) (Kd=1.5±0.6 nm ), was found to be normal on thrombin-stimulated platelets taken from a patient with grey platelet syndrome or a patient with Glanzmann thrombasthenia. LYP7 (IgG1, F(ab′)2 or Fab fragments) inhibited ristocetin-induced platelet aggregation of platelets in a dose-dependent fashion without affecting the binding of von Willebrand (vWf ) factor. However, agglutination of formaldehyde-fixed platelets induced by ristocetin was not affected by monoclonal antibody LYP7. In addition, the binding of thrombin-activated platelets to neutrophils was inhibited by monoclonal antibody LYP7. These results strongly suggest that P-selectin, by promoting cell–cell contact, may play an active role in platelet–platelet interactions. 相似文献
8.
B-chronic lymphocytic leukemia (CLL) patients frequently suffer from moderate to severe hypogammaglobulinemia. This complication is a serious cause of morbidity and mortality in this disorder. There is recent evidence that natural killer (NK) cells modulate B-cell immunoglobin (Ig) synthesis/secretion. The authors therefore evaluated the circulating NK cells from B-CLL patients on their ability to regulate mitogen-induced B-cell Ig synthesis. Blood, NK cells (CD16+, CD3-) from three B-CLL patients with hypogammaglobulinemia were able to clearly down-regulate the pokeweed mitogen (PWM)-induced-B-cell Ig secretion. In contrast, CD16+, CD3- cells from age-sex-matched controls or B-CLL patients with normal Ig were either nonregulatory or enhanced mitogen-induced B-cell Ig secretion. An alternative explanation for hypogammaglobulinemia in B-CLL patients is the immunomodulation of B- cell Ig production/secretion by CD16+, CD3- blood cells. 相似文献
9.
Gilles Morin Nadina Ortiz Bruechle Amrathlal Rabbind Singh Cordula Knopp Guillaume Jedraszak Miriam Elbracht Dominique Brémond‐Gignac Kathi Hartmann Henri Sevestre Peter Deutz Didier Hérent Peter Nürnberg Bernard Roméo Kerstin Konrad Michèle Mathieu‐Dramard Johannes Oldenburg Elisabeth Bourges‐Petit Yuequan Shen Klaus Zerres Halima Ouadid‐Ahidouch Jacques Rochette 《Human mutation》2014,35(10):1221-1232
Stormorken syndrome is a rare autosomal dominant disorder characterized by a phenotype that includes miosis, thrombocytopenia/thrombocytopathy with bleeding time diathesis, intellectual disability, mild hypocalcemia, muscle fatigue, asplenia, and ichthyosis. Using targeted sequencing and whole‐exome sequencing, we identified the c.910C > T transition in a STIM1 allele (p.R304W) only in patients and not in their unaffected family members. STIM1 encodes stromal interaction molecule 1 protein (STIM1), which is a finely tuned endoplasmic reticulum Ca2+ sensor. The effect of the mutation on the structure of STIM1 was investigated by molecular modeling, and its effect on function was explored by calcium imaging experiments. Results obtained from calcium imaging experiments using transfected cells together with fibroblasts from one patient are in agreement with impairment of calcium homeostasis. We show that the STIM1 p.R304W variant may affect the conformation of the inhibitory helix and unlock the inhibitory state of STIM1. The p.R304W mutation causes a gain of function effect associated with an increase in both resting Ca2+ levels and store‐operated calcium entry. Our study provides evidence that Stormorken syndrome may result from a single‐gene defect, which is consistent with Mendelian‐dominant inheritance. 相似文献
10.
Gilles Morin Nadina Ortiz Bruechle Amrathlal Rabbind Singh Cordula Knopp Guillaume Jedraszak Miriam Elbracht Dominique Brémond‐Gignac Kathi Hartmann Henri Sevestre Peter Deutz Didier Hérent Peter Nürnberg Bernard Roméo Kerstin Konrad Michèle Mathieu‐Dramard Johannes Oldenburg Elisabeth Bourges‐Petit Yuequan Shen Klaus Zerres Halima Ouadid‐Ahidouch Jacques Rochette 《Human mutation》2014,35(12):1542-1542