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WEIGUANG ZENG PIERRE-OLIVIER REGAMEY KEITH ROSE YUZHOU WANG ERNST BAYER 《Chemical biology & drug design》1997,49(3):273-279
The use of N, O-bisFmoc-N-(2-hydroxy-4-methoxybenzyl) amino acid derivatives in the synthesis of peptides with difficult sequences has already been described. With these amino acid derivatives the reversible protecting group 2-hydroxy-4-methoxybenzyl (Hmb) for the backbone amide bonds of peptide chains is introduced, and thus the aggregation due to hydrogen-bond interchain association is inhibited. This paper describes the synthesis and use of Fmoc-N-(2-hydroxy-4-methoxybenzyl)amino acid derivatives as an alternative means of introducing Hmb backbone protection. These new monoFmoc derivatives were obtained in higher yield than the bisFmoc derivatives. Coupling yields to the amino peptide resin were the same as those obtained with bisFmoc derivatives, under the TBTU/HOBt/DIEA conditions. We also compared different syntheses of a difficult peptide with the Fmoc approach [triple coupling, capping, use of chaotropic agents, backbone protection using monoFmoc (Hmb)Ala] and with optimized Boc chemistry. Both the backbone protection and optimized Boc chemistry approaches gave the desired product in excellent yield and purity. © Munksgaard 1997. 相似文献
3.
ARNAUD C. VERSCHUUR M.D. JANNES J.E. VAN EVERDINGEN M.D. ERNST B. COHEN M.D. ROB A.F.M. CHAMULEAU M.D. 《International journal of dermatology》1992,31(6):404-409
Before starting methotrexate therapy for cases of recalcitrant psoriasis, a liver biopsy has been usual in order to exclude cirrhosis and moderate or severe fibrosis, which are contraindications for methotrexate treatment. As mortality and morbidity of liver biopsy are not negligible, and as this invasive procedure is unpleasant for the patient and urges clinical admission, we evaluated the possibility of ruling out severe liver pathology by means of ultrasonography, which we compared to liver biopsy. We made this comparison by means of a decision tree. The advantages of this analysis are the clear definition of the decision problem and its alternatives, and the possibility of calculating the risk of each alternative, thus being able to choose the best diagnostic method. In this study, the results of various research groups are discussed, in which liver biopsy and liver ultrasound were compared. In our decision tree we used some of these results and other assumptions, based on comparable studies. We varied the biopsy mortality and the sensitivity of ultrasound to show the change in the risk of each alternative. Our analysis shows that the differences of expected values between the liver biopsy branch and the ultrasonography branch are relatively small. Therefore, we advise each center, which has at its disposal a specialist in liver ultrasonography, to re-evaluate its guidelines with regard to the detection of severe liver pathology before starting methotrexate for the treatment of psoriasis. 相似文献
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Ostial PV Isolation: 总被引:2,自引:0,他引:2
SABINE ERNST MATTHIAS ANTZ FEIFAN OUYANG THOMAS VOGTMANN MASAHIKO GOYA DIETMAR BÄNSCH ANSELM SCHAUMANN KARL-HEINZ KUCK 《Pacing and clinical electrophysiology : PACE》2003,26(7P2):1624-1630
Pulmonary vein (PV) isolation by elimination of spike potentials has been reported to cure drug refractory atrial fibrillation. Because of the heterogenous morphology of the PVs, sequential electroanatomic reconstruction of the PVs was performed in 39 patients (group A), who underwent subsequent PV isolation by interruption of all conductive myocardial fibers by distinct RF current applications using a "lasso" approach. In group B (157 patients), only biplane two-dimensional fluoroscopy was performed to guide the diagnostic and the ablation catheters. After reprocedures (in 7% of patients in group A and 22% of group B), which depicted a recurrence of a spike potential inside or at the ostium of >1 previously isolated PV in all restudied patients, stable sinus rhythm was documented in 69% of patients in group A and 60% of patients in group B. Reasons for the relapse of the previously eliminated spike potentials include a temporary ablation effect and a too distal interruption of the conducting myocardial fiber. Detailed knowledge of the individual three-dimensional morphology enhanced the clinical success rate of PV isolation but is time-consuming using CARTO (8.0 ± 1.7 vs 5.0 ± 1.6, P < 0.001) . Further technical improvement to fuse the individual three-dimensional anatomy and the electrophysiological markers to a composed "electroanatomic" map may overcome this limitation in the future. (PACE 2003; 26[Pt. II]:1624–1630) 相似文献
6.
Characterization of a soluble form of CD58 in synovial fluid of patients with rheumatoid arthritis (RA) 下载免费PDF全文
Reduced levels of a soluble form of the adhesion receptor and CD2 ligand CD58 (sCD58) were previously described in RA patients. In order to understand the biological significance of this finding we biochemically characterized sCD58 in RA and asked how well sCD58 binds to CD2. sCD58 concentrations were measured in serum and synovial fluid (SF) samples of RA patients by two ELISAs, one detecting domain 1 of CD58 (CD58-D1), and the other one the complete molecule (CD58-D1 + D2). Small amounts of split sCD58-D1 were found in most RA sera, but not SF. In addition, split sCD58-D2 was detected in SF by affinity chromatography, SDS–PAGE, and Western blotting. Gel filtration gave similar peaks at 95–125 kD for RA sera, SF, and normal serum. Binding of SF-sCD58 to the CD2+ Jurkat variant JBB1 or recombinant CD2 was stronger than urinary sCD58 and reached binding of oligomeric recombinant CD58 at low concentrations. In conclusion, sCD58-split products were found in RA sera and SF. At concentrations as they occur in vivo, SF-sCD58 binds to CD2 much more strongly than urinary sCD58. It is conceivable that locally released sCD58 blocks the CD2/CD58 interaction under physiological conditions. Insufficient release of sCD58, e.g. in synovitis, might result in T cell accumulation and perpetuation of inflammation. 相似文献
7.
Anti-CD2 (OX34) MoAb treatment of adjuvant arthritic rats: attenuation of established arthritis, selective depletion of CD4+ T cells, and CD2 down-modulation 总被引:2,自引:0,他引:2 下载免费PDF全文
J C HOFFMANN C HERKLOTZ H ZEIDLER B BAYER J WESTERMANN 《Clinical and experimental immunology》1997,110(1):63-71
Anti-CD2 MoAbs have previously been shown to induce tolerance and to block B cell differentiation, T cell and monocyte activation. Since these immune functions are important in joint inflammation, we asked whether administration of the anti-CD2 MoAb OX34 has a beneficial effect on established rat adjuvant arthritis, a model of human rheumatoid arthritis, and how it affects CD2-bearing leucocyte subsets. Female Lewis rats with established adjuvant arthritis received a total of 5 mg OX34 or isotype-matched control MoAb starting on day 15 after adjuvant injection. Weight and arthritis score (AS) were measured in a blinded fashion. Peripheral blood cells were analysed for numbers of leucocyte subsets at various time points. Animals were killed on day 30 and lymphatic organs were processed for immunohistology. Clinically, OX34 treatment led to increased body weight and reduced AS. Although OX34 binds to CD4+ and CD8+ T cells in a comparable fashion, OX34 treatment reduced CD4+ T cells, but not CD8+ T cells. Among CD4+ T cells CD45RC+ (‘naive’) T cells virtually disappeared; CD45RC− (‘recently activated’) T cells were slightly reduced. A reduction of CD4+ T cells was also found in the lung, liver, bone marrow, spleen and lymph nodes. Down-modulation of the CD2 molecule by OX34, again, affected CD4+ T cells, suggesting a specific signal for CD4+ but not CD8+ T cells. In conclusion, the anti-CD2 MoAb OX34 attenuates established rat adjuvant arthritis. In spite of similar binding to CD4+ and CD8+ T cells, OX34 depletes only CD4+ T cells and down-modulates the CD2 molecule on these cells. These results suggest a therapeutic benefit from CD2-directed therapy for chronic types of arthritis. 相似文献
8.
MUHLE H.; BELLMANN B.; CREUTZENBERG O.; DASENBROCK C.; ERNST H.; KILPPER R.; MACKENZIE J. C.; MORROW P.; MOHR U.; TAKENAKA S.; MERMELSTEIN R. 《Toxicological sciences》1991,17(2):280-299
Pulmonary Response to Toner upon Chronic Inhalation Exposurein Rats. MUHLE, H., BELLMANN, B., CREUTZENBERG, O., DASENBROCK,C., ERNST, H., KILPPER, R., MACKENZIE, J. C., MORROW, P., MOHR,U., TAKENAKA, S., AND MERMELSTEIN, R., Fundam. Appl. Toxicol.17, 280299. A chronic inhalation study of a test tonerwas conducted by exposure of groups of F-344 rats for 6 hr/day,5 days/week for 24 months The test toner was a special Xerox9000 type xerographic toner, enriched in respirable-sized particlescompared to commercial toner, such that it was about 35% respirableaccording to the ACGlH criteria. The target test aerosol exposureconcentrations were 0, 1.0 (low), 4.0 (medium), and 16.0 (high)mg/m3. Titamum dioxide (5 mg/m3) and crystalline silicon dioxide(1 mg/m3), used as negative and pasitive controls for fibrogenicity,were also evaluated. Inhalation of the test toner or the controlmaterials showed no signs of overt toxicity. Body weight, clinicalchemistry values, food consumption, and organ weights were normalin the toner- and TiO2-exposed groups, except for a 40% increasein lung weight in the toner highexposure group. All of the changesin the toner-exposed groups were restricted to the lungs orassociated lymph nodes. A chronic inflammatory response wasevident from the bronchoalveolar lavage parameters for the tonerhigh-exposure group. The incidence of primary lung tumors wascomparable among the three toner-exposed groups and the TiO2-exposed,and air-only controls, as well as consistent with historicalbackground levels A mild to moderate degree of lung fibrosiswas observed in 92% of the rats in the toner high-exposure group,and a minimal to mild degree of fibrosis was noted in 22% ofthe animals in the toner high-exposure group. The pulmonarychanges in the toner high-exposure group were smaller in magnitudethan those found in the crystalline silica-exposed group. Thecomparative fibrogenic potency of TiO2, toner, and SiO2 wasestimated to be 1:5:418 using a dasimetric model and assuminga common mechanistic basis. There were no pulmonary changesof any type at the toncr low-exposure level, which is most relevantin regard to potential human exposures The lung alterationsin the toner high-exposure group are interpreted in terms of"lung overloading," a generic response of the respiratory systemto saturation of its detoxification capacity. The maximum tolerateddose (MTD) criterion was met at the toner high (16 mg/m3)-exposurelevel. 相似文献
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The pathways for the reduction of methemoglobin to hemoglobin that aredependent upon the generation of reduced pyridine nucleotides were studiedin normal human erythrocytes, in erythrocytes deficient in G-6-PD activityand in erythrocytes of a subject with congenital methemoglobinemia. Reduction of methemoglobin, produced by treatment with nitrite, occurred atequivalent rates in normal and G-6-PD deficient erythrocytes, but failed tooccur in the erythrocytes of the patient with congenital methemoglobinemiaupon incubation with glucose or inosine. The DPNH-utilizing diaphorase-likesystem was normal in hemolysates of G-6-PD deficient erythrocytes, but wasmarkedly deficient in hemolysates of erythrocytes of the subject with congenital methemoglobinemia. The marked acceleration of methemoglobinreduction that occurred upon the addition of methylene blue to normal erythrocytes and to the erythrocytes of the woman with congenital methemoglobinemia did not occur with G-6-PD deficient erythrocytes. The TPNH-utilizing methemoglobin reductase system was normal in hemolysates oferythrocytes of the patient with congenital methemoglobinemia, but was reduced to about 50 per cent of normal activity in hemolysates of G-6-PD deficient erythrocytes.The reduction of methemoglobin to hemoglobin in intact normal and G-6-PD deficient human erythrocytes probably proceeds by way of a DPNH-utilizing, diaphorase-like system that is deficient in the erythrocytes of onetype of congenital methemoglobinemia. The TPNH-utilizing methemoglobinreductase appears to be a reserve system that requires an artificial electroncarrier, such as methylene blue, to become fully effective in reducing methemoglobin to hemoglobin. The TPNH-methemoglobin reductase system isimpaired in G-6-PD deficient erythrocytes not only because of a deficientsource of TPNH, but, perhaps, also because of a defect in this methemoglobinreductase system itself. Accepted on December 11, 1962 相似文献