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991.
Prolonged neutropenia due to antihuman neutrophil antigen 2 (CD177) antibody after bone marrow transplantation 下载免费PDF全文
Taizo Wada Satoshi Miyamoto Hiroyuki Okamoto Yusuke Matsuda Tomoko Toma Kohsuke Imai Masatoshi Takagi Tomohiro Morio Akihiro Yachie 《Pediatric blood & cancer》2017,64(7)
We describe a patient who presented with prolonged neutropenia due to anti‐human neutrophil antigen (HNA)‐2 (CD177) antibody after allogeneic bone marrow transplantation. A granulocyte immunofluorescence test showed bimodal expression of antineutrophil antibody that resulted from specific binding of anti‐HNA‐2 to CD177+ neutrophils from healthy donors. The patient did not respond to granulocyte colony stimulating factor, which is able to upregulate CD177 expression on neutrophils. The low percentage of CD177+ cells in the few remaining neutrophils supports the possibility of elimination of CD177‐upregulated neutrophils. These findings might explain an inferior response to neutrophil growth factors in neutropenia secondary to anti‐HNA‐2 antibody. 相似文献
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Yamamoto M Horie R Takeiri M Kozawa I Umezawa K 《Journal of medicinal chemistry》2008,51(18):5780-5788
Previously, we designed and synthesized a potent NF-kappaB inhibitor, DHMEQ. Although DHMEQ showed potent anti-inflammatory and anticancer activities in animals, its molecular target has not been elucidated. In the present study, its target protein was found to be p65 and other Rel homology proteins. We found that (-)-DHMEQ bound to p65 covalently with a 1:1 stoichiometry by conducting SPR and MALDI-TOF MS analyses. MS analysis of the chymotrypsin-digested peptide suggested the binding of (-)-DHMEQ to a Cys residue. Formation of Cys/(-)-DHMEQ adduct in the protein was supported by chemical synthesis of the adduct. Substitution of specific Cys in p65 and other Rel homology proteins resulted in the loss of (-)-DHMEQ binding. (-)-DHMEQ is the first NF-kappaB inhibitor that was proven to bind to the specific Cys by chemical methodology. These findings may explain the highly selective inhibition of NF-kappaB and the low toxic effect of (-)-DHMEQ in cells and animals. 相似文献
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Tashiro M Duan X Kato M Miyake M Watanuki S Ishikawa Y Funaki Y Iwata R Itoh M Yanai K 《British journal of clinical pharmacology》2008,65(6):811-821
AIMS
Antihistamines are frequently used for treating various allergic diseases, but often induce sedation. The degree of sedation can be evaluated by measuring histamine H1 receptor occupancy (H1RO) in the brain using positron emission tomography (PET). The aim was to measure H1RO of bepotastine, a new second-generation antihistamine, and to compare it with that of diphenhydramine.METHODS
Eight healthy male volunteers (mean age ± SD 24.4 ± 3.3 years) were studied after single oral administration of bepotastine (10 mg), diphenhydramine (30 mg) or placebo, by PET imaging with 11C-doxepin in a crossover study design. Binding potential ratio and H1ROs were calculated using placebo data and were compared between bepotastine and diphenhydramine in the anterior and posterior cingulate gyri (ACG and PCG, respectively), superior and inferior frontal cortices (SFC and IFC, respectively), orbitofrontal cortex (OFC), insular cortex (IC), lateral and medial temporal cortices (LTC and MTC, respectively), parietal cortex (PC), occipital cortex (OC) and sensorimotor cortex (SMC). Plasma concentration of each antihistamine was measured, and its correlation to H1RO was examined.RESULTS
H1RO after bepotastine treatment was significantly lower than that after diphenhydramine treatment in all cortical regions (P < 0.001). Mean H1ROs of bepotastine and diphenhydramine were 14.7% and 56.4%, respectively. H1ROs of both bepotastine and diphenhydramine correlated to their respective drug plasma concentration (P < 0.001).CONCLUSION
Oral bepotastine (10 mg), with its relatively low H1RO and thus minimal sedation, has the potential for use as a mildly or slightly sedative antihistamine in the treatment of various allergic disorders.WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT
- ‘Bepotastine besilate’ is a novel second-generation antihistamine developed in Japan and its antiallergic effects have already been demonstrated by various studies.
- However, only a few clinical studies regarding its sedative property are available.
- In addition, histamine H1 receptor occupancy (H1RO) of this new antihistamine has never been measured by positron emission tomography (PET).
WHAT THIS STUDY ADDS
- This paper provides the first measurement result of cerebral H1RO of bepotastine besilate (approximately 15%) as determined by PET.
- This result is in accordance with the clinical classification of bepotastine as a second-generation antihistamine.
- In addition, the relationship between subjective sleepiness and cerebral H1RO of this second-generation antihistamine is demonstrated for the first time using a placebo-controlled crossover study design.
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