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Defective Production (defective + production)

Distribution by Scientific Domains

Medical Sciences	75%

Selected Abstracts

Indirect study of thrombopoiesis(TPO, reticulated platelets, glycocalicin)in patients with hereditary macrothrombocytopenia

EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 3 2000
F. Fabris
To better understand the pathogenesis of thrombopoiesis in this hereditary thrombocytopenic disorder, we determined the percentage of reticulated platelets (RP), plasma glycocalicin (GC) and thrombopoietin (TPO) levels in 29 patients with CHMT, 23 patients with immune thrombocytopenic purpura (ITP), and 17 patients with thrombocytopenia secondary to decreased bone marrow megakaryocytes (hypoplasia). The % RP was similar in CHMT (2.27±1.33) and hypoplasia (1.98±1.35) patients and markedly lower than that in ITP patients (8.80±7.97; p<0.001), suggesting that the production of new platelets is reduced in CHMT. Plasma GC was within the normal range (0.84±0.16 ,g/mL) both in patients with CHMT (0.63±0.20 ,g/mL) and ITP (0.82±0.90 ,g/mL), while it was significantly decreased in patients with hypoplasia (0.16±0.04 ,g/mL; p<0.001). When the GC value was normalized for platelet count, the GC index was normal in CHMT patients (2.05±1.1) and in patients with hypoplasia (0.85±0.10) while it was significantly increased in ITP patients (10.88±18.00; p<0.001); thus, patients with CHMT seem to have a normal platelet turnover. TPO was significantly increased in CHMT (195±72 pg/ml) as compared with normal (80±53 pg/ml; p<0.002); however, the mean level was not as high as in ITP patients (345±167 pg/mL; p<0.001). This finding suggests that CHMT syndrome is not secondary to a defective production of TPO and that megakaryocyte mass is nearly normal. [source]

Mechanical behavior of recycled reinforced polyamide railway fasteners

POLYMER COMPOSITES, Issue 7 2010
José Antonio Casado
Modern railway tracks use short-fiber glass reinforced polyamide to inject insulating and mechanically resistant fasteners to connect the rails to the sleepers. Some of this material is later withdrawn, due either to defective production or to breakage in service. The recovery of the material for its later re-use would lead to a great saving, from both an environmental and an economic viewpoint. Mechanical recycling is a simple, economic process that only requires the crushing of the material and its subsequent molding, without the need for any chemical treatments. However, it has some drawbacks; as with any kind of recycling, there is a certain loss of material quality with some degradation of its properties. In this work, the physical and mechanical results for fasteners injected with recycled material are compared to others injected with pure material. The results show that the use of recycled fasteners is limited in-service by working conditions that increase the thermoplastic material temperature above its critical glass transition temperature, Tg. POLYM. COMPOS., 31:1142,1149, 2010. © 2009 Society of Plastics Engineers [source]

Reversing interleukin-2 inhibition mediated by anti,double-stranded DNA autoantibody ameliorates glomerulonephritis in MRL- lpr/lpr mice

ARTHRITIS & RHEUMATISM, Issue 8 2010
Ying-Chyi Song
Objective Our previous study demonstrated that anti,double-stranded DNA (anti-dsDNA) antibodies involved in lupus nephritis down-regulate the production of interleukin-2 (IL-2) in T cells, which in turn, contributes to the defective production of cytotoxic cells and to activation-induced cell death in vitro. To reveal novel molecular targets for lupus therapy, the molecular mechanisms of IL-2 down-regulation by anti-dsDNA were studied. Methods Anti-dsDNA monoclonal antibody (mAb) 9D7 was used to study the molecular mechanisms of IL-2 production in vitro. Treatment with arginine-rich peptide, a penetration inhibitor, was used to verify the effect of internalization of anti-dsDNA on the production of IL-2. The signaling pathway for IL-2 expression induced by anti-dsDNA was analyzed by using kinase inhibitors. The therapeutic effects of these inhibitors were evaluated in MRL- lpr/lpr mice. Results Inhibition of IL-2 production in activated Jurkat cells and human T cells pretreated with mAb 9D7 was reversed by treatment with the arginine-rich peptide. Levels of pAkt and phosphorylated glycogen synthase kinase 3 (pGSK-3) were reduced in activated Jurkat cells that had been pretreated with mAb 9D7. The inhibition of IL-2 production by mAb 9D7 was counteracted by pretreating the cells with LiCl (a GSK-3 inhibitor). However, IL-2 reduction was not recovered in the cells pretreated with ERK and JNK inhibitors. Furthermore, MRL- lpr/lpr mice injected with LiCl or with arginine-rich peptide restored the IL-2 production and reduced the manifestations of lupus. Conclusion These findings suggest that penetration of T cells by anti-dsDNA may inhibit IL-2 production by activating GSK-3. Moreover, blocking GSK-3 activation as well as inhibiting anti-dsDNA penetration is a potential therapeutic approach for lupus. [source]

HLA,DR alleles determine responsiveness to Borrelia burgdorferi antigens in a mouse model of self-perpetuating arthritis

ARTHRITIS & RHEUMATISM, Issue 12 2009
Bettina Panagiota Iliopoulou
Objective Arthritis is a prominent manifestation of Lyme disease, which is caused by infection with Borrelia burgdorferi (Bb). Chronic Lyme arthritis persisting even after antibiotic treatment is linked to HLA,DRB1*0401 (DR4) and related alleles. In contrast, patients whose Lyme arthritis resolves within 3 months postinfection show an increased frequency of HLA,DRB1*1101 (DR11). The aim of this study was to analyze the underlying mechanism by which HLA,DR alleles confer genetic susceptibility or resistance to antibiotic-refractory Lyme arthritis. Methods We generated DR11-transgenic (DR11-Tg) mice on a murine MHCII,/, background and compared their immune response to Bb antigens with the response of DR4-Tg mice after immunization with Bb outer surface protein A (OspA) or infection with live Bb. Results T cells from OspA-immunized and Bb-infected DR11-Tg mice had defective production of interferon-, as compared with those from DR4-Tg mice. In contrast, DR11-Tg mice developed higher titers of anti-OspA and anti-Bb antibodies, respectively, than did DR4-Tg mice. Consistent with this observation, we found that the Bb-infected DR11-Tg mice had a decreased spirochetal burden as compared with the DR4-Tg mice, as measured by quantitative polymerase chain reaction. Conclusion This study provides direct evidence that in the presence of HLA,DR11, the immune response against Bb antigens is directed toward a protective antibody response. In contrast, an inflammatory Th1 response is induced in the presence of DR4. These observations offer an explanation for the differential genetic susceptibility of DR4+ and DR11+ individuals to the development of chronic Lyme arthritis and, eventually, the progression to antibiotic-refractory Lyme arthritis. [source]