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11.
Structure-activity studies of 20-deoxo-20-amino derivatives of tylosin-related macrolides 总被引:1,自引:0,他引:1
H A Kirst K E Willard M Debono J E Toth B A Truedell J P Leeds J L Ott A M Felty-Duckworth F T Counter E E Ose 《The Journal of antibiotics》1989,42(11):1673-1683
Reductive amination of the C-20 aldehyde group of tylosin and related macrolides yielded a large series of derivatives with potentially useful antibiotic properties. Evaluation of these new compounds was conducted on the basis of: 1) Broad antimicrobial spectrum in vitro, with particular emphasis on inhibition of Pasteurella multocida and Pasteurella haemolytica; 2) in vivo efficacy, especially when given orally, against P. multocida in experimental infections in chicks; and 3) bioavailability after oral administration to laboratory animals. The most useful activity was found within a series of derivatives produced by reductive amination of desmycosin with secondary amines. 相似文献
12.
川芎嗪诱导大鼠骨髓间质干细胞分化为神经元样细胞的研究 总被引:26,自引:0,他引:26
目的用川芎嗪(ligustrazin hydrochloride)在体外定向诱导SD青年鼠骨髓间质干细胞(mesenchymal stem cells,rMSCs)分化为神经元样细胞。方法用低糖DMEM冲洗骨髓腔,收集骨髓细胞悬液,接种在塑料培养瓶中。经体外扩增、纯化,选用第5代后的骨髓间质干细胞进行诱导分化。用10μg/LbFcF预诱导24h,更换成含川芎嗪的无血清培养基DMEM诱导间质干细胞分化为神经元样细胞。用免疫组织化学SABC法鉴定神经丝蛋白(NF—M)、神经元特异性烯醇化酶(NSE)、巢蛋白(nestin)、微管联合蛋白-2(MAP-2)、生长相关蛋白-43(GAP-43)、胶质纤维酸性蛋白(GFAP)的表达。结果第5代间质干细胞形态达到均一,呈梭形。用川芎嗪诱导15min到3h,间质干细胞胞体逐渐增大,并伸出细长突起形似神经元样细胞。免疫组织化学显示NF-M、NSE、nestin、MAP-2和GAP-43表达阳性,而GFAP阴性。对照组上述染色均为阴性。结论川芎嗪可诱导骨髓间质干细胞分化为神经元样细胞。 相似文献
13.
Androgen receptor YAC transgenic mice carrying CAG 45 alleles show trinucleotide repeat instability 总被引:1,自引:15,他引:1
La Spada AR; Peterson KR; Meadows SA; McClain ME; Jeng G; Chmelar RS; Haugen HA; Chen K; Singer MJ; Moore D; Trask BJ; Fischbeck KH; Clegg CH; McKnight GS 《Human molecular genetics》1998,7(6):959-967
X-linked spinal and bulbar muscular atrophy (SBMA) is caused by a CAG
repeat expansion in the first exon of the androgen receptor (AR) gene.
Disease-associated alleles (37-66 CAGs) change in length when transmitted
from parents to offspring, with a significantly greater tendency to shift
size when inherited paternally. As transgenic mice carrying human AR cDNAs
with 45 and 66 CAG repeats do not display repeat instability, we attempted
to model trinucleotide repeat instability by generating transgenic mice
with yeast artificial chromosomes (YACs) carrying AR CAG repeat expansions
in their genomic context. Studies of independent lines of AR YAC transgenic
mice with CAG 45 alleles reveal intergenerational instability at an overall
rate of approximately 10%. We also find that the 45 CAG repeat tracts are
significantly more unstable with maternal transmission and as the
transmitting mother ages. Of all the CAG/CTG repeat transgenic mice
produced to date the AR YAC CAG 45 mice are unstable with the smallest
trinucleotide repeat mutations, suggesting that the length threshold for
repeat instability in the mouse may be lowered by including the appropriate
flanking human DNA sequences. By sequence-tagged site content analysis and
long range mapping we determined that one unstable transgenic line has
integrated an approximately 70 kb segment of the AR locus due to
fragmentation of the AR YAC. Identification of the cis - acting elements
that permit CAG tract instability and the trans -acting factors that
modulate repeat instability in the AR YAC CAG 45 mice may provide insights
into the molecular basis of trinucleotide repeat instability in humans.
相似文献
14.
Genetic mapping of the human homologue (T) of mouse T(Brachyury) and a search for allele association between human T and spina bifida 总被引:3,自引:0,他引:3
15.
Summary A case of a 44-year-old woman with a solitary pulmonary coin lesion is presented. Histologic study of this nodule revealed a normal intraparenchymal pulmonary lymph node. A review of the literature discusses the incidence and characteristics of this entity.
Nud lymphatique intrapulmonaire: revue de la littérature. A propos d'un cas
Résumé L'observation d'un cas de lésion nodulaire du poumon est rapportée chez une femme de 44 ans. L'étude histologique du nodule a révélé un nud lymphatique intrapulmonaire normal. La revue de la littérature apprécie l'incidence et les caractéristiques de cette localisation.相似文献
16.
The role of size, sequence and haplotype in the stability of FRAXA and FRAXE alleles during transmission 总被引:2,自引:5,他引:2
Murray A; Macpherson JN; Pound MC; Sharrock A; Youings SA; Dennis NR; McKechnie N; Linehan P; Morton NE; Jacobs PA 《Human molecular genetics》1997,6(2):173-184
Factors involved in the stability of trinucleotide repeats during
transmission were studied in 139 families in which a full mutation,
premutation or intermediate allele at either FRAXA or FRAXE was
segregating. The transmission of alleles at FRAXA, FRAXE and four
microsatellite loci were recorded for all individuals. Instability within
the minimal and common ranges (0-40 repeats for FRAXA, 0-30 repeats for
FRAXE) was extremely rare; only one example was observed, an increased in
size at FRAXA from 29 to 39 repeats. Four FRAXA and three FRAXE alleles in
the intermediate range (41-60) repeats for FRAXA, 31-60 for FRAXE) were
unstably transmitted. Instability was more frequent for FRAXA intermediate
alleles that had a tract of pure CGG greater than 37 although instability
only occurred in two of 13 such transmissions: the changes observed were
limited to only one or two repeats. Premutation FRAXA alleles over 100
repeats expanded to a full mutation during female transmission in 100% of
cases, in agreement with other published series. There was no clear
correlation between haplotype and probability of expansion of FRAXA
premutations. Instability at FRAXA or FRAXE was more often observed in
conjunction with a second instability at an independent locus suggesting
genomic instability as a possible mechanism by which at least some FRAXA
and FRAXE mutations arise.
相似文献
17.
Since exogenous hemin has been shown to exert a variety of stimulatory effects on erythroid cells, including the augmentation of hemoglobin synthesis, we determined its effect on early stages of erythroid development by employing clonal cells assays. The addition of hemin at a concentration of 2 X 10(-4) M to cultures of normal murine marrow substantially increased the observed number of primitive BFU-E, which was in contrast to its lack of an effect on more mature erythroid colony-forming cells. This cell-specific enhancement of primitive BFU-E resulted in marrow frequencies equivalent to or exceeding those reported in the presence of "burst-promoting activity." In the presence of hemin, the number of BFU-E was also observed to be linearly related to the number of cells plated at very low plating densities, and the cell titration curve was observed to extrapolate to the origin. The evidence suggests that hemin may be a primary growth regulator of early developmental stages of erythroid progenitor cells. 相似文献
18.
Assessment of the mutagenicity of dichloroacetic acid in lacI transgenic B6C3F1 mouse liver 总被引:2,自引:0,他引:2
Dichloroacetic acid (DCA) is a chlorination byproduct found in finished
drinking water. When administered in drinking water this chemical has been
shown to produce hepatocellular adenomas and carcinomas in B6C3F1 mice over
the animal's lifetime. In this study, we investigated whether mutant
frequencies were increased in mouse liver using treatment protocols that
yielded significant tumor induction. DCA was administered continuously at
either 1.0 or 3.5 g/l in drinking water to male transgenic B6C3F1 mice
harboring the bacterial lacI gene. Groups of five or six animals were
killed at 4, 10 or 60 weeks and livers removed. At both 4 and 10 weeks of
treatment, there was no significant difference in mutant frequency between
the treated and control animals at either dose level. At 60 weeks, mice
treated with 1.0 g/l DCA showed a 1.3-fold increase in mutant frequency
over concurrent controls (P = 0.05). Mice treated with 3.5 g/l DCA for 60
weeks had a 2.3-fold increase in mutant frequency over the concurrent
controls (P = 0.002). The mutation spectrum recovered from mice treated
with 3.5 g/l DCA for 60 weeks contained G:C-->A:T transitions (32.79%)
and G:C-->T:A transversions (21.31%). In contrast, G:C-->A:T
transitions comprised 53.19% of the recovered mutants among control
animals. Although only 19.15% of mutations among the controls were at T:A
sites, 32.79% of the mutations from DCA-treated animals were at T:A sites.
This is consistent with the previous observation that the proportion of
mutations at T:A sites in codon 61 of the H-ras gene was increased in
DCA-induced liver tumors in B6C3F1 mice. The present study demonstrates
DCA-associated mutagenicity in the mouse liver under conditions in which
DCA produces hepatic tumors.
相似文献
19.
Fatty acid balance studies in term infants fed formula milk containing long-chain polyunsaturated fatty acids 总被引:1,自引:0,他引:1
C Morgan L Davies F Corcoran J Stammers J Colley SA Spencer D Hull 《Acta paediatrica (Oslo, Norway : 1992)》1998,87(2):136-142
Long-chain polyunsaturated fatty acids (LCP) are thought to be required for optimal nervous system development in the newborn. A commercial milk formula containing LCP (Aptamil-LCP) with a fatty acid profile closely resembling breast milk, has recently been introduced for term infants. The absorption of fatty acids in term infants was examined in a double-blind randomized controlled trial comparing Aptamil-LCP ( n = 20) and standard Aptamil ( n = 20). Formula-fed newborn infants were studied from birth for 14 d. Fat balances (3 d) were performed from d 10. A 3-d stool collection was performed from d 10 in a parallel breastfed group ( n = 21). Plasma samples were taken on d 6. Median fat excretion (mg kg−1 ) was 897.1, 615.0 and 355.2 with Aptamil, Aptamil-LCP and breastfeeding, respectively. The median total fat absorption coefficient in Aptamil-LCP-fed infants was higher than in those fed standard Aptamil ( p < 0:01). These findings were accounted for by differences in the excretion and absorption of long-chain saturated fatty acids (C14:0, C16:0 and C18:0). Higher fat excretion was associated with bulkier and firmer stools. Only trace amounts of LCP were detected in the stools of all groups. This accounted for less than 4% of dietary intake in Aptamil-LCP-fed infants. No differences in the utilization of LCP from Aptamil-LCP and breast milk feeding were apparent. Plasma phospholipid fatty acid composition data reflected differences in dietary LCP intake. Thus, PL LCP levels were highest in the breastfed infants and lowest in the Aptamil-fed infants, with values for the Aptamil-LCP-fed group falling in between. 相似文献
20.
Characterization of the insulin-like growth factor axis in a human hepatoma cell line (PLC) 总被引:4,自引:0,他引:4
Scharf JG; Schmidt-Sandte W; Pahernik SA; Ramadori G; Braulke T; Hartmann H 《Carcinogenesis》1998,19(12):2121-2128