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221.
3-甲基芬太尼衍生物立体异构体的 QSAR 研究 总被引:3,自引:0,他引:3
用比较分子力场分析(CoMFA)方法研究了3-甲基芬太尼和羟甲芬太尼立体异构体的三维定量构效关系(3D-QSAR)。所得CoMFA-QSAR模型有很好的预测能力(γ2cros-validated=0.716,noptimalcomponent=5,γ2conventional=0.999,s=0.052,F=1305.1),模型中,被研究化合物的构象可能就是其活性构象。以AM1方法进行量子化学计算,获得上述可能活性构象的结构参数及空间位置参数。基于这些参数,用偏最小二乘法(PLS)获得了被研究化合物的QSAR方程。所得PLS-QSAR模型具有较好的预测能力,并且显示被研究化合物的镇痛活性取决于分子中负电性的哌啶氮原子(NPA)净电荷以及哌啶氮原子、羰基氧原子、1-β-苯环、4-N-苯环、3-甲基和2′-羟基的空间位置。 相似文献
222.
Yang YC; Kovacic S; Kriz R; Wolf S; Clark SC; Wellems TE; Nienhuis A; Epstein N 《Blood》1988,71(4):958-961
As demonstrated by long-range mapping of restriction endonuclease recognition sequences and genomic cloning, we found that the human genes encoding interleukin 3 (IL 3) and granulocyte/macrophage colony- stimulating factor (GM-CSF) are tandemly arrayed on the long arm of chromosome 5, separated by 9 kilobases (kb) of DNA. This close physical linkage of genes with similar structure and biologic function suggests that these cytokines may have evolved from a common ancestral gene. This linkage in evolution of two relatively divergent genes further implies that some of the other lymphokine and cytokine genes that appear to share as much or more sequence similarity than do IL 3 and GM- CSF may be distantly related members of a cytokine gene family. 相似文献
223.
复方紫草油纱条在糖尿病皮肤溃疡及褥疮中的应用 总被引:4,自引:1,他引:3
0 引言 我们对 9例糖尿病皮肤溃疡及褥疮患者采用了自制复方紫草油纱条治疗的方法 ,疗效满意 ,现报道如下 :1 材料和方法1.1 一般资料 本组患者 9(男 6 ,女 3)例 .年龄 2 9~ 6 5岁 .尾骶部褥疮 4例 (1例并发左右足跟部褥疮 ) ;髋关节处褥疮 1例 ;小腿部溃疡 2例 ;足背部溃疡 1例 (同时并发小指末节皮肤溃疡 ) ;背部溃疡 1例 .1.2 复方紫草油纱条的制作 采用以紫草为主辅加十三味中草药 ,制成复方紫草油膏 ,后溶化浸入无菌纱条即可 .1.3 治疗方法 1彻底清创 ,暴露出新鲜组织 ;2褥疮有水疱时 ,先予以无菌操作下抽吸 ;3将双层以上复… 相似文献
224.
Localization of myotonic dystrophy protein kinase in human and rabbit tissues using a new panel of monoclonal antibodies 总被引:1,自引:4,他引:1
There is considerable confusion in the literature about the size of the
myotonic dystrophy protein kinase (DMPK) and its localization within
tissues. We have used a new panel of monoclonal antibodies (mAbs) to begin
to resolve these issues, which are important for understanding the possible
role of DMPK in myotonic dystrophy. Antisera raised against the catalytic
and coil domains of DMPK recognized a major 55 kDa protein and a minor
72-80 kDa doublet on western blots of human skeletal muscle. Ten mAbs, five
against the catalytic domain and five against the coil region, recognized
only the 72-80 kDa doublet. The 72 kDa protein was present in all tissues
tested, whereas the 80 kDa component was variably expressed, mainly in
skeletal and cardiac muscles. The 72 kDa protein was absent in a DMPK
knockout mouse and was greatly increased in a transgenic mouse
overexpressing human DMPK, confirming its identity as authentic DMPK. Two
mAbs against the catalytic domain recognized only the more abundant 55 kDa
protein, which was found only in skeletal muscle. Nine out of 10 mAbs
located DMPK to intercalated discs in human heart, an affected tissue in
myotonic dystrophy. However, co-localization of DMPK with acetylcholine
receptors at neuromuscular junctions was not observed with any of the mAbs.
Subcellular fractionation and sedimentation analysis suggest that a major
proportion of the DMPK in skeletal muscle and brain is cytosolic.
相似文献
225.
Linkage between markers in the vicinity of the uncoupling protein 2 gene and resting metabolic rate in humans 总被引:17,自引:1,他引:17
Bouchard C; Perusse L; Chagnon YC; Warden C; Ricquier D 《Human molecular genetics》1997,6(11):1887-1889
The recent cloning of a gene that codes for a novel uncoupling protein,
UCP2, which is expressed in a wide range of adult human tissues, has raised
the possibility that it may be involved in regulation of energy balance. To
explore this concept we have investigated potential linkage relationships
between three microsatellite markers which encompass the UCP2 gene location
on 11q13 with resting metabolic rate (RMR), body mass index, percentage
body fat (%FAT) and fat mass (FM) in 640 individuals from 155 pedigrees
from the Quebec Family Study. Using a linkage analysis strategy based on
sibling, avuncular, grandparental and cousin pairs, strong evidence of
linkage was found between the marker D11S911 (P = 0.000002) and RMR, with
more moderate evidence for D11S916 (P = 0.006) and D11S1321 (P = 0.02).
Suggestive evidence of linkage was also observed between D11S1321 and %FAT
(P = 0.04) and FM (P = 0.02). It is concluded that the three markers
encompassing the UCP2 locus and spanning a 5 cM region on 11q13 are linked
to resting energy expenditure in adult humans. The evidence is strong
enough to warrant a search for DNA sequence variation in the gene itself.
相似文献
226.
Kim YC Fung Edouard Nice Ilka Priebe Damien Belobrajdic Aloke Phatak Leanne Purins Bruce Tabor Celine Pompeia Trevor Lockett Timothy E Adams Antony Burgess Leah Cosgrove 《World journal of gastroenterology : WJG》2014,20(4):888-898
Colorectal cancer(CRC)is the second most common cause of cancer-related death worldwide and places a major economic burden on the global health care system.The time frame for development from premalignant to malignant disease typically spans 10-15 years,and this latent period provides an ideal opportunity for early detection and intervention to improve patient outcomes.Currently,early diagnosis of CRC is hampered by a lack of suitable non-invasive biomarkers that are clinically or economically acceptable for populationbased screening.New blood-based protein biomarkers for early detection of CRC are therefore urgently required.The success of clinical biomarker discovery and validation studies is critically dependent on understanding and adjusting for potential experimental,analytical,and biological factors that can interfere with the robust interpretation of results.In this review we outline some important considerations for research groups undertaking biomarker research with exemplars from our studies.Implementation of experimental strategies to minimise the potential effects of these problems will facilitate the identification of panels of biomarkers with the sensitivity and specificity required for the development of successful tests for the early detection and surveillance of CRC. 相似文献
227.
Erythrocyte glutathione (GSH) can be rapidly depleted by incubating the cells with 1-chloro-2,4-dinitrobenzene (CDNB), which forms 2,4- dinitrophenyl-S-glutathione with GSH through the reaction catalyzed by glutathione S-transferase. GSH-CDNB conjugate thus formed stays undegraded within the erythrocytes. This indicates that in the erythrocytes, mercapturic acid pathway is inoperative. Depletion of GSH in the intact erythrocytes by CDNB results in rapid oxidation of large amounts of hemoglobin to methemoglobin. When glutathione S-transferase- free hemolysate of erythrocytes is incubated with CDNB, the depletion of GSH as well as methemoglobin formation are minimal. Glutathione peroxidase and glutathione reductase activities of the erythrocytes are not affected by CDNB. These studies provide a specific enzymatic method for rapid removal of erythrocyte GSH and also indicate that GSH is vital in maintaining a reduced environment within the erythrocytes. 相似文献
228.
Age-specific regulation of clotting factor IX gene expression in normal and transgenic mice 总被引:3,自引:1,他引:3
Boland EJ; Liu YC; Walter CA; Herbert DC; Weaker FJ; Odom MW; Jagadeeswaran P 《Blood》1995,86(6):2198-2205
Factor IX (FIX), a circulating serine protease that serves as an essential component of the blood coagulation pathway, has been shown to increase with age in humans. We show here that murine FIX mRNA and activity levels also increase with age. Furthermore, one form of hemophilia B, hemophilia B Leyden, which is caused by mutations within the promoter region of the FIX gene, has a distinct age-dependent phenotype. To determine the source of the age-related increases in FIX gene expression, we have analyzed the regulation of the normal FIX gene promoter and FIX Leyden gene promoter with the +13 mutation during aging by generating transgenic mice that contain the -189 to +21 bp promoter segment ligated to a chloramphenicol acetyltransferase reporter gene. We have established that the normal FIX promoter and the Leyden promoter transgenes are expressed in a tissue-specific manner in vivo. The normal FIX promoter transgene does not show any differences in the pattern of expression with age or sex of the organism, whereas the Leyden promoter transgene showed age-dependent male-specific expression. This is the first demonstration of the FIX Leyden phenotype in a transgenic mouse model. 相似文献
229.
Hereditary persistence of fetal hemoglobin or (delta beta)o- thalassemia: three types observed in South-Chinese families 总被引:2,自引:0,他引:2
Hematological and hemoglobin composition data, and results from extensive gene mapping, using a battery of restriction enzymes and probes, have been used to distinguish different types of hereditary persistence of fetal hemoglobin (HPFH) (or delta beta-thal) among three Chinese families from the southern part of China. The first (Family Z) is an A gamma-(delta beta)+-HPFH without a detectable deletion and may be the same as, or similar to, that described by Farquhar et al (Am J Hum Genet 35:611, 1983). The second (Family C) resembles a G gamma(A gamma delta beta)o-thalassemia and is characterized by a large deletion of DNA originating 3' to the G gamma globin gene and extending beyond sequences recognized by the pRK28 probe. Data from various digests indicate possible differences in the 3' end of the deletion when compared with data for some other types of G gamma(A gamma delta beta)o- thalassemia, described by Trent et al (Br J Haematol 57:279, 1984). The third (Family Zh) concerns a G gamma A gamma(delta beta)+-HPFH, which is characterized in heterozygotes by a fetal hemoglobin level of 20% to 25% with a G gamma value averaging 60% and by the absence of any DNA deletion detectable by extensive gene mapping analyses. The C----G mutation at position 202 5' to the G gamma globin gene [characteristic for the high G gamma-(delta beta)+-HPFH (Proc Natl Acad Sci USA 81:4894, 1984; Blood 64:1292, 1984)] was absent, but the Xmn I site at position 158 5' to the G gamma globin gene [characteristic for a modest increase in G gamma values and thus and increased G gamma to A gamma ratio (Blood)] was present. No indication has yet been obtained explaining the elevation in both G gamma and A gamma chains; haplotyping showed that the chromosome carrying this G gamma A gamma(delta beta)+ determinant is unusual among the Chinese population. 相似文献
230.
We studied the erythroid burst-promoting activity (BPA) of recombinant human granulocyte/macrophage colony-stimulating factor (GM-CSF) and Interleukin-3 (IL-3) with two experimental approaches. First we studied the effects of polyclonal antisera prepared against human GM-CSF and gibbon IL-3 on colony formation from 1,000 bone marrow null cells/dish in serum-containing culture. Both GM-CSF and IL-3 independently enhanced erythroid burst formation; however, IL-3 showed more BPA activity than GM-CSF. These data are in agreement with an emerging view that the primary targets of IL-3 are primitive progenitors and that the targets of GM-CSF are intermediate progenitors, including erythroid burst-forming units (BFU-E). The proliferation of one population of BFU- E was independent of GM-CSF or IL-3. To characterize this population of BFU-E further, we developed a serum-free culture assay for the purified progenitors by incorporating insulin-like growth factor-1 (IGF-1) to the serum-free medium. The development of erythroid bursts was supported by IL-3, IGF-1, and erythropoietin (Ep) in a serum-free culture system and to a lesser extent by the combination of GM-CSF, IGF- 1, and Ep. Although the burst-promoting ability of GM-CSF and IL-3 was again demonstrated in this system, unlike serum-containing culture Ep alone did not support burst formation. These results indicate that when fetal calf serum (FCS) is present, the culture system contains BPA that is not GM-CSF or IL-3. 相似文献