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21.
V G Matassa F J Brown P R Bernstein H S Shapiro T P Maduskuie L A Cronk E P Vacek Y K Yee D W Snyder R D Krell 《Journal of medicinal chemistry》1990,33(9):2621-2629
The dissociation constants (KB) at the LTD4 receptor on guinea pig trachea of a series of monocyclic and bicyclic cyclopentylurethane and cyclopentylacetamide N-arylsulfonyl amides have been measured. The KB was found to be remarkably tolerant of changes in the electronic constitution and lipophilicity of the bicyclic ring system (template). Thus, N-[4[[6-[[(cyclopentyloxy)carbonyl]amino]benzimidazol-1- yl]methyl]-3-methoxybenzoyl]benzenesulfonamide (11a) and N-[4-[[5-[[(cyclopentyloxy)carbonyl]amino]benzo[b]thien-3- yl]methyl]-3-methoxybenzoyl]benzene-sulfonamide (25a) had closely similar affinities (pKB, 9.20 and 9.31, respectively; LTE4 as agonist). It has been shown that the hetero-ring of the template need not be aromatic in order to achieve high affinity, since indoline 31 and 2,3-dihydrobenz-1,4-oxazines 37a-c had pKBs greater than 9. Further, it has been shown that an o-aminophenone (see 42 and Figure 3) can function as a template; the template in 42 [see iii] is bicyclic by virtue of the presence of an intramolecular hydrogen bond. In contrast, when the template is a phenyl ring (48), receptor affinity is markedly reduced. These findings support the notion that central bicyclic ring system in this family of peptidoleukotriene antagonists is a molecular feature which helps to preorganize the acylamino and acidic chains and thereby facilitate the molecular recognition event. 相似文献
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N-acetylaspartate is an axon-specific marker of mature white matter in vivo: a biochemical and immunohistochemical study on the rat optic nerve. 总被引:5,自引:0,他引:5
Carl Bjartmar Jan Battistuta Nobuo Terada Erica Dupree Bruce D Trapp 《Annals of neurology》2002,51(1):51-58
Axonal pathology is a major cause of neurological disability in multiple sclerosis. Axonal transection begins at disease onset but remains clinically silent because of compensatory brain mechanisms. Noninvasive surrogate markers for axonal injury are therefore essential to monitor cumulative disease burden in vivo. The neuronal compound N-acetylaspartate, as measured by magnetic resonance spectroscopy, is currently the best and most specific noninvasive marker of axonal pathology in multiple sclerosis. The possibility has been raised, however, that N-acetylaspartate is expressed also by oligodendroglial lineage cells. In order to investigate N-acetylaspartate specificity for white matter axons, transected rat optic nerves were analyzed by high-performance liquid chromatography and immunohistochemistry. In transected adult nerves, N-acetylaspartate and N-acetyl aspartylglutamate decreased in concordance with axonal degeneration and were undetectable 24 days posttransection. Nonproliferating oligodendrocyte progenitor cells, oligodendrocytes, and myelin were abundant in these axon-free nerves. At 24 days posttransection, N-acetylaspartate was increased (42%; p = 0.02) in nontransected contralateral nerves. After transection at postnatal day 4, total N-acetylaspartate decreased by 80% (P14; p = 0.002) and 94% (P20; p = 0.003). In these developing axon-free nerves, 25 to 33% of oligodendrocyte progenitor cells were proliferating. These data validate magnetic resonance spectroscopy measurements of N-acetylaspartate as an axon-specific monitor of central nervous system white matter in vivo. In addition, the results indicate that neuronal adaptation can increase N-acetylaspartate levels, and that 5 to 20% of the N-acetylaspartate in developing white matter is synthesized by proliferating oligodendrocyte progenitor cells. 相似文献
24.
Infective conjunctivitis and corneal scarring in three brothers with sex linked hypogammaglobulinaemia (Bruton''s disease).
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T T Hansel D P O''Neill M L Yee J M Gibson R A Thompson 《The British journal of ophthalmology》1990,74(2):118-120
The ocular findings in three brothers with Bruton's disease are reported. All three boys had purulent conjunctivitis, but the two older brothers also developed marked corneal scarring with visual impairment. Haemophilus influenzae was cultured from conjunctival swabs; it was resistant to neomycin but sensitive to chloramphenicol. Tear analysis showed that the three subjects had normal levels of lysozyme but no detectable IgA. 相似文献
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Although antibiotics are widely used in an attempt to decrease the incidence of infections after facial fractures, no systematic prospective study of their efficacy has been performed. In this study, all adult patients with facial fractures who had not received antibiotics were asked to participate in a clinical trial. There were 101 patients with facial fractures enrolled into the study and randomized prospectively into two groups. One group received no antibiotics. The other group received cefazolin sodium, 1 g intravenously, one hour prior to the surgical procedure, and a similar dose eight hours later. Of the 101 patients enrolled in the study, 79 had mandibular fractures, 18 had zygoma fractures, and four had Le Fort fractures. When all facial fractures were considered, perioperative intravenous cefazolin reduced the incidence of postoperative infections; 42.2% in the no-antibiotic group became infected, and 8.9% in the antibiotic group became infected. On the basis of this study, we conclude that cefazolin, used perioperatively, diminished the incidence of postoperative infections in facial fractures. 相似文献
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David S. Yee Joel Gelman Douglas W. Skarecky Thomas E. Ahlering 《Journal of robotic surgery》2007,1(2):151-154
Fossa navicularis strictures following radical prostatectomy are reported infrequently. We recently experienced a series of
fossa strictures following robotic-assisted laparoscopic prostatectomy (RLP). We describe herein our experience to prevent
fossa strictures and to determine its etiologic factors. From June 2002 to May 2006, 424 patients underwent robotic-assisted
laparoscopic prostatectomy with the da Vinci surgical system. Fossa strictures were diagnosed based on the acute onset of
obstructive voiding symptoms and bougie calibration. During our series, we switched from the intra-operative use of an 18
French (F) catheter to that of a 22 F one to avoid inadvertent stapling of the urethra when dividing the dorsal venous complex.
After we observed a high incidence of fossa strictures, we reverted back to 18 F catheters during surgery. All patients had
an 18 F catheter indwelling for 1 week after surgery. Parameters were evaluated using Fisher’s exact test and Student’s t-test for means. The 18 F catheter group of patients (n = 293) developed one fossa stricture, whereas the 22 F catheter group (n = 131) developed nine fossa strictures (P < 0.01). The fossa stricture rate in the 18 F group was 0.3% versus 6.9% in the 22 F group. The two groups had no differences
in age, body mass index, cardiovascular disease, American Urological Association symptom score, urinary bother score, preoperative
prostate-specific antigen, operative time, estimated blood loss, cautery use, prostate size, or catheterization time. Based
on these results, a larger urethral catheter size – 20 F versus 18 F – during the intra-operative dissection would appear
to increase the risk for fossa stricture by more than 20-fold.
Statement of disclosure Dr. Thomas Ahlering is a meeting participant and lecturer for Intuitive Surgical Corp. The other authors have no direct or
indirect commercial financial incentives associated with publishing the article. No research or project support funding was
received. 相似文献
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