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61.
62.
C B Xue E Eriotou-Bargiota D Miller J M Becker F Naider 《The Journal of biological chemistry》1989,264(32):19161-19168
An analog of alpha-factor, the Saccharomyces cerevisiae tridecapeptide mating pheromone (Trp-His-Trp-Leu-Gln-Leu-Lys-Pro-Gly-Gln-Pro-Met-Tyr), in which the side chains of Lys7 and Gln10 were covalently linked, was synthesized using solid phase methodologies. The yield of the purified cyclic analog cyclo7,10[Nle12]alpha-factor was 30%, and its structure was verified by amino acid analysis, peptide sequencing, fast atom bombardment-mass spectrometry, and proton nuclear magnetic resonance spectroscopy. Cyclo7,10[Nle12]alpha-factor caused growth arrest and morphological alterations in S. cerevisiae MATa cells qualitatively identical to those induced by linear pheromone and was one-fourth to one-twentieth as active as the linear alpha-factor depending upon the S. cerevisiae strain tested. Consistent with the relative activities of the linear and cyclic peptides, binding competition studies indicated that cyclo7,10[Nle12]alpha-factor had approximately 20-40-fold less affinity for the alpha-factor receptor. Hydrolysis of the cyclic peptide by the target cells did not lead to opening of the ring and was less rapid than that of linear alpha-factor. The alpha-factor antagonist des-Trp1-[Ala3,Nle12]alpha-factor reversed the activity of the cyclic analog, and cyclo7,10[Nle12]alpha-factor was not active at the restrictive temperature in a temperature-sensitive receptor mutant. These results support the conclusion that the cyclic alpha-factor occupies the same binding site within the receptor as is occupied by the natural pheromone. The cyclic alpha-factor represents a rare example of an agonist among covalently constrained congeners of small linear peptide messengers. 相似文献
63.
The teratogenic effect of ethanol in the C57BL/6J mouse can be attenuated by pretreatment with aspirin (ASA). One prominent effect of ASA is to inhibit prostaglandin (PGE) and thromboxane (TXB2) production. We examined the effect of in vivo ethanol exposure on PGE and TXB2 production in a uterine-embryo tissue sample of C57BL/6J mice either before or after in vivo ASA pretreatment on day 10 of gestation. Ethanol increased both PGE and TXB2 production by approximately 20%. ASA caused a marked reduction of PGE and TXB2 in both control and ethanol groups by approximately 80-90%. The mouse strain, gestation time, and study parameters used in this study were the same as in the previously reported ASA attenuation of the teratogenic effect of ethanol. Therefore, the present data add additional support to the hypothesis that prostaglandin and/or thromboxane production may be involved in at least some aspects of fetal alcohol syndrome. 相似文献
64.
65.
Although Montgomery's tubercles are often prominent structures on the areola, little attention has been paid to their reconstruction. Present techniques for nipple-areola reconstruction result in a flat-appearing surface that is usually not characteristic of a normal areola with its projecting Montgomery's tubercles. We describe a technique for creating Montgomery's tubercles that has resulted in a more normal-appearing nipple-areola complex and a higher degree of patient satisfaction. 相似文献
66.
Down''s Syndrome Individuals Begin Life with Normal Levels of Brain Cholinergic Markers 总被引:3,自引:1,他引:2
Stephen Kish Harry Karlinsky Lawrence Becker Joseph Gilbert Michelle Rebbetoy Li-Jan Chang Linda DiStefano Oleh Hornykiewicz 《Journal of neurochemistry》1989,52(4):1183-1187
We measured the activities of the cholinergic marker enzymes choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) in autopsied brains of seven infants (age range 3 months to 1 year) with Down's syndrome (DS), a disorder in which virtually all individuals will develop by middle age the neuropathological changes of Alzheimer's disease accompanied by a marked brain cholinergic reduction. When compared with age-matched controls cholinergic enzyme activity was normal in all brain regions of the individuals with infant DS with the exception of above-normal activity in the putamen (ChAT) and the occipital cortex (AChE). Our neurochemical observations suggest that DS individuals begin life with a normal complement of brain cholinergic neurons. This opens the possibility of early therapeutic intervention to prevent the development of brain cholinergic changes in patients with DS. 相似文献
67.
68.
Alpha subunit variants of the human glycine receptor: primary structures, functional expression and chromosomal localization of the corresponding genes. 总被引:31,自引:10,他引:21
G Grenningloh V Schmieden P R Schofield P H Seeburg T Siddique T K Mohandas C M Becker H Betz 《The EMBO journal》1990,9(3):771-776
Two cDNAs encoding variants (alpha 1 and alpha 2) of the strychnine binding subunit of the inhibitory glycine receptor (GlyR) were isolated from a human fetal brain cDNA library. The predicted amino acid sequences exhibit approximately 99% and approximately 76% identity to the previously characterized rat 48 kd polypeptide. Heterologous expression of the human alpha 1 and alpha 2 subunits in Xenopus oocytes resulted in the formation of glycine-gated strychnine-sensitive chloride channels, indicating that both polypeptides can form functional GlyRs. Using a panel of rodent-human hybrid cell lines, the gene encoding alpha 2 was mapped to the short arm (Xp21.2-p22.1) of the human X chromosome. In contrast, the alpha 1 subunit gene is autosomally located. These data indicate molecular heterogeneity of the human GlyR at the level of alpha subunit genes. 相似文献
69.
Replication of a plasmid lacking the normal site for initiation of one strand. 总被引:2,自引:1,他引:1 下载免费PDF全文
The origin of replication of the plasmid R1162 contains an initiation site for the synthesis of each DNA strand. When one of these sites (oriL) is deleted, synthesis on the corresponding strand is no longer initiated efficiently in vitro by the R1162-encoded replication proteins, and the plasmid is no longer stably maintained in the cell. However, in vivo the two strands of the plasmid duplex molecule are active at a similar level as templates for DNA synthesis, and newly synthesized copies of each strand are incorporated into daughter molecules at a similar rate. No secondary, strong initiation sites on the delta oriL strand were detected in the region of the origin. The delta oriL plasmid induces the SOS response, and this is important for plasmid maintenance even in a recombination-proficient strain. Our results indicate that an SOS-induced host system can maintain an R1162 derivative lacking one of its initiation sites. 相似文献
70.
James D. Pancook Jürgen C. Becker Stephen D. Gillies R. A. Reisfeld 《Cancer immunology, immunotherapy : CII》1996,42(2):88-92
A major problem in the treatment of solid tumors is the eradication of established, disseminated metastases. Here we describe
an effective treatment for established experimental hepatic metastases of human neuroblastoma in C. B.-17 scid/scid mice. This was accomplished with an antibody-cytokine fusion protein, combining the unique targeting ability of antibodies
with the multifunctional activity of cytokines. An anti-(ganglioside GD2) antibody (ch14.18) fusion protein with interleukin-2
(ch14.18-IL2), constructed by fusion of a synthetic sequence coding for human interleukin-2 (IL-2) to the carboxyl end of
the Cγ1 gene of ch14.18, was tested for its therapeutic efficacy against xenografted human neuroblastoma in vivo. The ch14.18-IL2
fusion protein markedly inhibited growth of established hepatic metastases in SCID (severe combined immunodeficiency) mice
previously reconstituted with human lymphokine-activated killer cells. Animals treated with ch14.18-IL2 showed an absence
of macroscopic liver metastasis. In contrast, treatment with combinations of ch14.18 and recombinant IL2 at dose levels equivalent
to the fusion protein only reduced the tumor load. Survival times of SCID mice treated with the fusion protein were more than
double that of control animals. These results demonstrate that an immunotherapeutic approach using a cytokine targeted by
an antibody to tumor sites is highly effective in eradicating the growth of established tumor metastases.
Received: 7 November 1995 / Accepted: 15 December 1995 相似文献