排序方式: 共有34条查询结果,搜索用时 15 毫秒
11.
Kain R Exner M Brandes R Ziebermayr R Cunningham D Alderson CA Davidovits A Raab I Jahn R Ashour O Spitzauer S Sunder-Plassmann G Fukuda M Klemm P Rees AJ Kerjaschki D 《Nature medicine》2008,14(10):1088-1096
Pauci-immune focal necrotizing glomerulonephritis (FNGN) is a severe inflammatory disease associated with autoantibodies to neutrophil cytoplasmic antigens (ANCA). Here we characterize autoantibodies to lysosomal membrane protein-2 (LAMP-2) and show that they are a new ANCA subtype present in almost all individuals with FNGN. Consequently, its prevalence is nearly twice that of the classical ANCAs that recognize myeloperoxidase or proteinase-3. Furthermore, antibodies to LAMP-2 cause pauci-immune FNGN when injected into rats, and a monoclonal antibody to human LAMP-2 (H4B4) induces apoptosis of human microvascular endothelium in vitro. The autoantibodies in individuals with pauci-immune FNGN commonly recognize a human LAMP-2 epitope (designated P(41-49)) with 100% homology to the bacterial adhesin FimH, with which they cross-react. Rats immunized with FimH develop pauci-immune FNGN and also develop antibodies to rat and human LAMP-2. Finally, we show that infections with fimbriated pathogens are common before the onset of FNGN. Thus, FimH-triggered autoimmunity to LAMP-2 provides a previously undescribed clinically relevant molecular mechanism for the development of pauci-immune FNGN. 相似文献
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The presence of hydroxyproline, and the determination of the ratio of the secondary amino acids proline to hydroxyproline, in amino acid hydrolysates specifically identifies collagen and collagen peptides. o-Phthalaldehyde, and then 9-fluorenylmethyl chloroformate, were used to carry out sequential prederivatization of amino acid hydrolysates in an in-line high-performance liquid chromatography sample loop. After derivatization, reversed-phase high-performance liquid chromatography with a C-18 ODS Hypersil cartridge column was used to resolve the hydroxyproline and proline from all primary amino acids, with resolution and detection of hydroxyproline and proline within 2.0 and 2.8 min, respectively, at concentrations in the range of picomoles per microliter of derivatized amino acid. The assay has a turnaround time of 10.75 min. 相似文献
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Agai-Csongor E Domány G Nógrádi K Galambos J Vágó I Keserű GM Greiner I Laszlovszky I Gere A Schmidt E Kiss B Vastag M Tihanyi K Sághy K Laszy J Gyertyán I Zájer-Balázs M Gémesi L Kapás M Szombathelyi Z 《Bioorganic & medicinal chemistry letters》2012,22(10):3437-3440
Medicinal chemistry optimization of an impurity isolated during the scale-up synthesis of a pyridylsulfonamide type dopamine D(3)/D(2) compound (1) led to a series of new piperazine derivatives having affinity to both dopamine D(3) and D(2) receptors. Several members of this group showed excellent pharmacokinetic and pharmacodynamic properties as demonstrated by outstanding activities in different antipsychotic tests. The most promising representative, 2m (cariprazine) had good absorption, excellent brain penetration and advantageous safety profile. Based on its successful clinical development we are looking forward to the NDA filing of cariprazine in 2012. 相似文献
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Borza I Kolok S Galgóczy K Gere A Horváth C Farkas S Greiner I Domány G 《Bioorganic & medicinal chemistry letters》2007,17(2):406-409
A novel series of kynurenic acid amides, ring-enlarged derivatives of indole-2-carboxamides, was prepared and identified as in vivo active NR2B subtype selective NMDA receptor antagonists. The synthesis and SAR studies are discussed. 相似文献
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Borza I Kolok S Gere A Agai-Csongor E Agai B Tárkányi G Horváth C Barta-Szalai G Bozó E Kiss C Bielik A Nagy J Farkas S Domány G 《Bioorganic & medicinal chemistry letters》2003,13(21):3859-3861
A novel series of indole-2-carboxamide derivatives was prepared and identified as NR2B selective NMDA receptor antagonists. The influence of the number and position of OH groups on the indole skeleton as well as the substitution of the piperidine ring on the biological activity of the compounds was studied. 相似文献
18.
Selma Tobudic Veronika Plunger Gere Sunder-Plassmann Markus Riegersperger Heinz Burgmann 《PloS one》2012,7(9)
Renal transplant recipients are at increased risk of developing invasive pneumococcal diseases but may have poor response to the 23-valent pneumococcal polysaccharide vaccine (PPV). It may be possible to enhance immunogenicity by priming with 7-valent pneumococcal conjugate vaccine (7vPnC) and boosting with PPV 1 year later. In a randomized single-blind, controlled study, adult recipients of renal transplants received either 7nPVC or PPV followed by PPV 1 year later. The vaccine response was defined as 2-fold increase in antibody concentration from baseline and an absolute post-vaccination values ≥1 µg/ml. The primary endpoint was vaccine response of the primed group (7vPnC/PPV) compared with single PPV vaccination. Antibody concentrations for 10 serotypes were measured at baseline, 8 weeks after first vaccination, before second vaccination, and 8 weeks after second vaccination. Of 320 screened patients, 80 patients were randomized and 62 completed the study. Revaccination with PPV achieved no significant increase of immune response in the 7vPnC/PPV group compared with the single PPV recipients A response to at least 1 serotype was seen in 77.1% of patients who received 7vPnC and 93.1% of patients who received PPV (P = 0.046). After second vaccination response to at least 1 serotype was seen in 87.5% patients of 7vPnC/PPV group and 87.1% patients of PPV group (non significant p). The median number of serotypes eliciting a response was 3.5 (95% CI 2.5–4.5) in the 7vPnC/PPV group versus 5 (95% CI 3.9–6.1) in the PPV group (non-significant p). Immunogenicity of pneumococcal vaccination was not enhanced by the prime–boost strategy compared with vaccination with PPV alone. Administration of a single dose of PPV should continue to be the standard of care for adult recipients of renal transplants.
Trial Registration
EudraCT 2007-004590-25. 相似文献19.
Oxamides as novel NR2B selective NMDA receptor antagonists 总被引:1,自引:0,他引:1
Barta-Szalai G Borza I Bozó E Kiss C Agai B Proszenyák A Keseru GM Gere A Kolok S Galgóczy K Horváth C Farkas S Domány G 《Bioorganic & medicinal chemistry letters》2004,14(15):3953-3956
A novel series of oxamides derived from indole-2-carboxamides was identified as potent NR2B selective NMDA receptor antagonists. Several members of this group showed good analgesic activity in the mouse formalin test. 相似文献
20.
Sunder-Plassmann N Sarli V Gartner M Utz M Seiler J Huemmer S Mayer TU Surrey T Giannis A 《Bioorganic & medicinal chemistry》2005,13(22):6094-6111
The mitotic kinesin Eg5 (or KSP) is a crucial player in the development and function of the mitotic spindle. Inhibition of this protein leads to cell cycle arrest and apoptosis without interfering with other microtubule-dependent processes. Therefore, it is a potential target in cancer therapy. Here, we report the synthesis and biological evaluation of a small library of molecules based on the structure of the known Eg5 inhibitor HR22C16. One of these derivatives (compound trans-24) proved to be a potent and specific Eg5 inhibitor. 相似文献